Human Exposure

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National Toxicology Program. Report on Carcinogens Monograph on Cobalt and Cobalt Compounds That Release Cobalt Ions In Vivo: RoC Monograph 06 [Internet]. Research Triangle Park (NC): National Toxicology Program; 2016 Apr.

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Report on Carcinogens Monograph on Cobalt and Cobalt Compounds That Release Cobalt Ions In Vivo: RoC Monograph 06 [Internet].

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2Human Exposure

This section describes cobalt mining and production (Section 2.1); use (Section 2.2); recycling of electronic and electrical waste (Section 2.3); biomonitoring and environmental monitoring studies and methods to measure exposure to cobalt and cobalt compounds (Section 2.4); and potential exposure in the workplace (Section 2.5), from surgical implants (Section 2.6), from other sources such as food, consumer products, tobacco, and medical products (Section 2.7), and from the environmental exposure (Section 2.9). The material presented in Sections 2.1 through 2.8 is summarized in Section 2.9. Studies of cobalt alloys were not considered informative for either animal tumor studies or human carcinogenicity studies because they are not useful for evaluating potential carcinogenic effects from cobalt per se; cobalt alloys are a source of exposure to humans, and thus are discussed in this section.

2.1. Mining and Production

Cobalt is most often found in ores associated with copper or nickel, but may also be a by-product of zinc, lead, and platinum-group metals (CDI 2006; Davis 2000). Cobalt-containing ores often contain arsenic, such as safflorite, CoAs₂; skutterudite, CoAs₃; erythrite, Co₃(AsO₄)₂•8H₂O; and glaucodot, CoAsS (ATSDR 2004; CDI 2006; Davis 2000). The largest cobalt reserves are in the Congo (Kinshasa), Australia, Cuba, Zambia, Canada, Russia, and New Caledonia (Shedd 2014b). Most U.S. cobalt deposits are in Minnesota, but other important deposits are in Alaska, California, Idaho, Missouri, Montana, and Oregon. Except for Idaho and Missouri, future production from these deposits would be as a by-product of another metal.

Except for a negligible amount of by-product cobalt produced as an intermediate product from mining and refining platinum-group metals ore, the United States did not refine cobalt in 2012 (Shedd 2014a). Since 2009, no cobalt has been sold from the National Defense Stockpile. In 2012, 2,160 metric tons of cobalt was recycled from scrap. Cobalt has not been mined in the United States in over 30 years (ATSDR 2004); however, a primary cobalt mine, mill, and refinery are currently being established in Idaho that will produce more than 1,500 tons of high-purity cobalt metal annually to capitalize on increasing cobalt demand driven in part by growth in “green” energy technology (e.g., rechargeable batteries for electric and hybrid electric vehicles or portable electronics applications (Farquharson 2015; Mining Technology Market Customer Insight 2015; Rufe 2010). Based on a presentation dated May 2015, preliminary work on the site has been completed (Formation Metals Inc. 2015).

Cobalt and several cobalt compounds are high-production-volume chemicals based on their production or importation into the United States in quantities of 1 million pounds or more per year. Table 2-1 shows U.S. cobalt and cobalt compound production volumes for 2012 that exceed 100,000 pounds per year; the highest United States production volume is for cobalt (7440-48-4) (23,384,002 lb.). Table 2-2 lists recent U.S. imports and exports of cobalt and cobalt compounds; the highest import value is for “unwrought cobalt excluding alloys, including powders” (16,151,599 lb.) and the highest export value is for “cobalt, wrought, and articles thereof” (4,841,750 lb.).

Table 2-1

U.S. Cobalt Compounds Production Volumes for 2012 Exceeding 100,000 Pounds per Year^a.

Table 2-2

U.S. Imports and Exports of Cobalt Compounds for 2013 (Converted from kg by NTP).

2.2. Use

Cobalt is used in numerous commercial, industrial, and military applications. On a global basis, the largest use of cobalt is in rechargeable battery electrodes; however, rechargeable battery production in the United States has been very limited (NIST 2005).

In 2012, the reported U.S. consumption of cobalt was approximately 8,420 metric tons (Shedd 2014a) for the uses shown below in Table 2-3.

Table 2-3

2012 U.S. Consumption and Use Pattern for Cobalt.

The main uses of cobalt can be grouped into the following general categories: metallurgical; cemented carbides and bonded diamonds; chemicals; and electronics and “green” energy (CDI 2006). Cobalt nanoparticles are used for medical applications (e.g., sensors, MRI contrast enhancement, drug delivery); nanofibers and nanowires also are being used for industrial applications.

Metallurgical uses of cobalt include use in superalloys (Davis 2000; IARC 1991); magnetic alloys, low expansion alloys, nonferrous alloys, steels, coatings, and bone and dental prostheses (CDI 2006; Davis 2000; IARC 1991; Ohno 2010). Support structures for heart valves are also manufactured from cobalt alloys (IARC 1991).

Cemented tungsten carbides (“hard metals”) are composites of tungsten carbide particles (either tungsten carbide alone or in combination with smaller amounts of other carbides) with metallic cobalt powder as a binder, pressed into a compact, solid form at high temperatures by a process called sintering (IARC 1991; NTP 2009). Cobalt is also used in diamond tools from steel with microdiamonds impregnated into a surface cobalt layer (CDI 2006; IARC 2006)).

Chemical uses of cobalt compounds include as pigments for glass, ceramics, and enamels, as driers for paints, varnishes, or lacquers, as catalysts, as adhesives and enamel frits (naphthenate, stearate, oxide), as trace mineral additives for animal diets, and in rechargeable batteries (see Section 2.3 (ATSDR 2004; CDI 2006; IARC 1991; WHO 2006) (see Table 2-4). Compounds of commercial importance are the oxides, hydroxide, chloride, sulfate, nitrate, phosphate, carbonate, acetate, oxalate, and other carboxylic acid derivatives (IARC 1991). A past use of cobalt (as cobalt sulfate) was as an additive in some beers to increase the stability of the foam (NTP 1998).

Table 2-4

Chemical Uses for Representative Inorganic and Organic Cobalt Compounds.

Due to increased demand for portable rechargeable electronic devices, one of the fastest growth areas for cobalt use worldwide is in high-capacity, rechargeable batteries (CDI 2006; Davis 2000; Shedd 2014a). Cobalt is used in nickel-cadmium, nickel-metal hydride, and lithium-ion battery technologies. Applications for batteries containing cobalt compounds include portable computers, mobile telephones, camcorders, toys, power tools, and electric vehicles. Cobalt is also used in integrated circuit contacts and leads and in the production of semiconductors (CDI 2006; IARC 1991).

Cobalt is the key element in several forms of “green” energy technology applications including gas-to liquid (GTL) and oil desulfurization, coal-to liquid (CTL), clean coal, solar panels, wind and gas turbines, and fuel cells (Rufe 2010). Research is ongoing on use of cobalt-based catalysts in sunlight-driven water splitting to convert solar energy into electrical and chemical energy (Deng and Tüysüz 2014).

2.3. Recycling of Electronic and Electrical Waste

Electronic and electrical waste (i.e., e-waste) includes components of electrical and electronic equipment such as rechargeable batteries. Automobile rechargeable battery recycling is generally considered to be in its infancy, though more developed for nickel-metal hydride batteries than for lithium-ion batteries (Evarts 2013; Gaines 2014).

Recycling for Li-ion batteries is more difficult because these batteries have various active material chemistries (e.g., lithium cobalt oxide, lithium manganese oxide, lithium nickel manganese cobalt oxide, etc.), contain a wider variety of materials in each cell, are not currently subject to recycling regulations, and will not be ending their useful lives in large numbers for about 10 years (Cadex Eletronics Inc. 2015; Gaines 2014). Further, recent trends to reduce costs of battery manufacturing and to optimize performance (e.g., safety, durability, and output) have lead manufacturers to seek other non-cobalt-based constituents (e.g., iron phosphate, manganese spinel, and nickel manganese), which might reduce the economic incentive for recycling (Retriev Technologies 2015).

2.4. Biomonitoring and Environmental Monitoring for Cobalt

Information on biomonitoring and environmental monitoring for cobalt discussed below includes evidence of exposure (Section 2.4.1) and exposure surrogates and analytical methods (Section 2.4.2).

2.4.1. Evidence of Exposure

Evidence for widespread exposure to cobalt and cobalt compounds comes from biological monitoring data measuring cobalt levels in urine, blood, hair, nails, and tissues in individuals exposed to cobalt from occupational and non-occupational sources (see Table B-2 and Table B-3 for levels reported in these studies, source of exposure, and geographical location and Figure 2-1 and Figure 2-2). Several publications measured trace metals (e.g., heavy metals and essential metals) in tissue from cancer patients with a referent group or tissue. Several clinical surveys have compared levels of cobalt in cancer patients and non-cancer patients (see Table B-4). Several of the studies are of people residing in the United States, and thus demonstrate U.S. exposure. Data are reported for both a surrogate of recent (urine) and longer term (hair) exposure to cobalt.

Figure 2-1

Cluster Graph of Urine Cobalt Levels from Different Sources of Exposure

Figure 2-2

Cluster Graphs of Cobalt Levels in Hair

Studies measuring cobalt in the urine of people exposed to cobalt from different sources indicate that the highest levels were generally seen in workers and patients with failed hip implants; with lower levels of exposure in patients with normal implants, people potentially exposed to cobalt from the environment, or in the general public (source of exposure unknown). (See Figure 2-1, which depicts the mean [or median] levels of urinary cobalt in these populations from the studies reported in Table B-2.) The geometric mean urinary cobalt concentration for the U.S. general public for the most recent National Health and Nutrition Examination Survey (NHANES) year (Centers for Disease Control and Prevention (CDC) and National Center for Health Statistics (NCHS) 2011) for which data are available is 0.326 μg/L; urinary cobalt measurements in the U.S. general public have remained consistent since 1999, with the geometric mean values ranging from 0.316 to 0.379 μg/L (CDC 2015).

Reported mean levels of cobalt in hair are highest among some workers and among patients with unstable hip implants (Figure 2-2). Cobalt levels in samples from patients with stable hip implants are next highest, with levels taken from people at risk of environmental exposure and the general public being the lowest. Measurements of cobalt in hair in the latter groups overlap significantly; while one study indicates that cobalt levels among environmentally exposed populations are similar to levels in workers.

2.4.2. Exposure Surrogates and Analytical Methods

Exposure Surrogates

Urinary cobalt is considered a good indicator of absorbed cobalt (IARC 2006; WHO 2006), especially from recent exposures (ATSDR 2004). Urinary and blood cobalt levels are more reflective of recent exposure for soluble compounds than less soluble compounds (ATSDR 2004). Although investigators have reported measurements of cobalt in whole blood, plasma, and serum, no consensus seems to exist for which of these provides the best relationship with levels of exposure to cobalt.

Because hair fixes trace elements in a permanent, chemically homogeneous matrix, hair samples reflect a time-integrated exposure (i.e., current and past exposure levels) over the previous few months, depending on the length of the hair sample (Suzuki and Yamamoto 1982) and hair metal contents provides a better estimate than blood in assessing the environmental risk to toxic metals for infrequent and highly variable exposures (Bax 1981; Petering et al. 1973). The average concentration of cobalt in hair is over 100 times greater than that in blood (Underwood 1977). Average metal concentration can be obtained by measuring bulk concentration from a length of hair equal to a few weeks’ growth, by measuring the variation along the length of long hair equal to several months (Suzuki and Yamamoto 1982), or by taking periodic samples over time (Laker 1982).

Toenail clippings reflect time-integrated exposure occurring in the timeframe of 12 to 24 months prior to clipping, and thus are useful biomarkers of exposure when a single sample is assumed to represent long-term exposure (Fleckman 1985; He 2011). However, toenails generally provide larger samples and represent more distant past exposures because they take longer to grow out. Nails are considered to be relatively sheltered from environmental contaminants (relative to hair, which, though formed from the same keratinous tissue of nail, can be contaminated by dyeing, bleaching, and permanent waving). Toenails are also more convenient to collect and store than blood (Garland et al. 1993). However, nails can become contaminated through the use of nail polishes, some medications, and use of contaminated cutters to produce clippings (He 2011).

The source of exposure for urinary cobalt levels in the general public (see Figure 2-1) is unknown. Likewise, the source of exposure for the general public is unknown for the exposure surrogates (e.g., hair and nails).

Analytical Methods

Analytical methods for cobalt in biological materials include graphite furnace atomic absorption spectrometry (GF-AAS), inductively coupled plasma-atomic emission spectrometry (ICP-AES), differential pulse cathodic stripping voltammetry (DPCSV), and colorimetric determination (ATSDR 2004). Technical improvements using the Zeeman background correction in GF-AAS have increased specificity and lowered the background (see IUPAC guidelines in Cornelis et al. 1995). The colorimetric method generally has limited utility because it has poor sensitivity (Alessio and Dell’Orto 1988). The ICP-AES method is used by NIOSH for exposure to elements in blood and urine (NIOSH 1994b), and NHANES uses a related method of inductively coupled plasma-mass spectrometry (ICP-MS) for urine heavy metals. With the exception of the colorimetric method, these methods require wet (acid) digestion followed by flame ionization to liberate free cobalt ions for detection of total cobalt. Thus, in any biological sample, the original form of the cobalt, whether inorganic cobalt or part of an organic molecule like vitamin B₁₂, cannot be determined with these methods (IARC 2006; WHO 2006).

The analytical method for air sampling (NIOSH Method 7027) involves collecting the sample on a 0.8 μm pore size cellulose ester membrane filter and analyzing the sample using a flame atomic absorption spectrophotometer. This is an elemental analysis and is not compound specific (NIOSH 1994a). For surface sampling, the analytical method (NIOSH Method 9102) involves collecting a wipe sample on a pre-packaged moist disposable towelette (e.g., Wash ‘n Dri or ASTM equivalent per ASTM E1792-01) and analyzing the sample using ICP-AES. Likewise, this method also is an elemental analysis and is not compound specific (NIOSH 2003).

2.5. Characterization of Exposure in the Workplace

The primary route of occupational exposure to cobalt is via inhalation of dust, fumes, or mists or gaseous cobalt carbonyl; however, dermal contact with hard metals and cobalt salts can result in systemic uptake. Occupational exposure to cobalt occurs during (1) the refining of cobalt, (2) the production of cobalt powders, (3) use in the hard metal, diamond tool, and alloy industries (including the production and use of these cobalt-containing products), use to make chemicals, pigments, and electronics, and (4) in the recycling of electronics. Workers regenerating spent catalysts may also be exposed to cobalt sulfides. U.S. occupational exposure data are available for the following industries: metallurgical; cemented carbides and bonded diamonds; chemicals and pigments; and electronics, “green” energy, and recycling.

Occupational exposure has been documented by measurements of cobalt in ambient workplace air, in worker blood and urine, and in deceased worker lung tissue (ATSDR 2004; CDC 2013; IARC 1991; 2006). The NIOSH National Occupational Exposure Survey (NOES) estimated that approximately 386,500 workers were potentially exposed to cobalt and cobalt compounds (NIOSH 1990). The survey was conducted from 1981 to 1983, and the NOES database was last updated in July 1990.

Air levels for workplace for cobalt production, metallurgical uses of cobalt, cemented carbides (hard metals) and bonded diamonds, chemical and pigments, and electronics, “green” energy, and recycling are listed in Table 2-5. Exposure data for cobalt levels in urine and blood are listed in Table B-2, and levels in hair and nails are in Table B-3. The findings for these media are briefly summarized below.

Table 2-5

Workplace Air Levels of Cobalt.

2.5.1. Cobalt Production (Metals and Salts)

Cobalt concentrations in workplace air have been reported to range from 2 to 50,000 μg/m³ from hydrometallurgical purification (to produce cobalt metal, cobalt oxide, and cobalt salt products), battery recycling (to recover cobalt for reuse), and cobalt compound (acetate, chloride, nitrate, and sulfate) production. Worker urinary cobalt for these facilities ranged from 1.6 to 2,038 μg/g creatinine (IARC 2006). The mean urinary and serum or blood cobalt levels reported in Table B-2 generally fall in the range of 10s or 100s of μg/L (or μg/g creatinine). Data for cobalt in hair and nails for cobalt production are limited, but one study listed in Table B-3 reported a mean level of almost 100 μg/g for hair compared with unexposed individuals in the same study with 0.38 μg/g.

Available data on emissions of cobalt from electrochemical production of cobalt (in nickel refining plants) indicate that exposure to cobalt is expected to be low. Based on analysis of nearly 3,500 personal breathing zone samples analyzed for cobalt at a Norwegian nickel refinery, the median 8-hour time-weighted arithmetic average exposures were less than 0.1 μg/m³ (Grimsrud et al. 2005). A European report of processes to produce nickel and cobalt noted that total emissions of cobalt to air from grinding/leaching, solvent extraction, and final recovery or transformation were 0.9 kilograms per metric ton of cobalt produced (IPPC 2014).

2.5.2. Metallurgical-related Industries

Occupational exposure results from production and use (e.g., welding, grinding, and sharpening) of cobalt alloys. Concentrations of cobalt in workplace air of facilities producing and using Stellite have been reported to range from 9 to several hundred micrograms per cubic meter (IARC 2006). Urinary cobalt levels in the 10s of μg/g (reported as μg/mg but considered a typographical error) creatinine for a metallurgical site in the United States but no blood levels were identified for these activities.

U.S. cobalt occupational exposure level data available from NIOSH HETA surveys for metallurgical-related industries indicate the following: workplace air levels range from not detected to 32,000 μg/m³; workplace arithmetic mean, median, or geometric mean urine levels range from 0.6 μg/L or μg/g creatinine to 50.4 μg/L or μg/g creatinine (it is generally accepted that 1 L of urine contains 1 g of creatinine); surface wipe levels range from 2.1 μg/100 cm² to 760 μg/100 cm²; and the one reported value for cobalt in bulk samples of work materials was 0.08% (Beaucham et al. 2014; Daniels et al. 1986; Decker 1991; Deitchman et al. 1994; Deng et al. 1990; Hervin and Reifschneider 1973; Kiefer et al. 1994; Marsh and Esmen 2007; McCleery et al. 2001; NIOSH 1972).

2.5.3. Cemented Carbides and Bonded Diamonds

Exposure to cobalt can occur in hard-metal production, processing, and use and during the maintenance and re-sharpening of hard-metal tools and blades. Air levels of cobalt vary across different stages of the hard-metals manufacturing process, with levels for operations involving cobalt metal powder often reaching maximum levels between 1,000 and 10,000 μg/m³ (NTP 2009). Continuous recycling of coolants used during the grinding of hard-metal tools after sintering and during maintenance and re-sharpening has been reported to increase concentrations of dissolved cobalt in the metal-working fluid, which can be a source of exposure to ionic cobalt in aerosols from the coolants (IARC 2006). Wet grinding processes are reported to produce higher cobalt concentrations than dry grinding processes due to coolant mist emissions.

Diamond polishers inhale metallic cobalt, iron, and silica from the use of cobalt discs to polish diamond jewels. Cobalt concentrations in workplace air have been reported to range from 0.1 to 45 μg/m³ in diamond jewel polishing and as high as 690 μg/m³ in wood and stone cutting (air concentrations dropped to 115 μg/m³ after implementation of ventilation system improvements in the wood and stone cutting factory) (IARC 2006).

A number of data points are available for cobalt in urine and blood or serum for these occupational exposures (see Table B-2). Most mean urinary cobalt values were between 1 and 100 μg/L or μg/g creatinine but some values up to 500 μg/L were reported for some operations involving cobalt powder. Blood cobalt generally falls in the range of 1 to 50 μg/L for exposures in these industries. The highest levels of blood cobalt were reported for a hard-metal manufacturing facility in Italy which also reported levels of approximately 50 μg/g for hair and toenails; other sites ranged down to 1 μg/g or less.

U.S. cobalt occupational exposure level data available from NIOSH Hazard Evaluation and Technical Assistance (HETA) surveys for cemented carbides and bonded diamonds indicate the following: workplace air levels range from not detected to approximately 1,620 μg/m³; workplace arithmetic mean, median, or geometric mean urine levels range from 9.6 μg/L or μg/g creatinine to 27 μg/L or μg/g creatinine (it is generally accepted that 1 L of urine contains 1 g of creatinine); the one reported geometric mean blood cobalt level was 2.0 μg/L; surface wipe levels range from not detected to 4,400 μg/100 cm²; skin (i.e., hand or neck) wipe levels range from 2 μg/sample to approximately 22,330 μg/sample (from charging operations in a cemented tungsten carbide plant); geometric mean exhaled breath condensate levels range from 5.5 μg/L to 6.2 μg/L; cobalt in bulk samples of work materials ranges from 0.033% to 8.97%; cobalt in settled dust samples from work areas ranges from 0.2% to 2% (Bryant et al. 1987; Burr et al. 1988; Burr and Sinks 1988; Edmonds et al. 1981; Kerndt et al. 1986; McManus 1982; Sahakian et al. 2009; Salisbury and Seligman 1987; Tharr and Singal 1987). One extreme value of 438,000 μg/m³ was reported for weighing and mixing operations in a plant in the United States (Sprince et al. 1984).

2.5.4. Chemicals and Pigments

Cobalt concentrations in workplace air at Danish porcelain factories using cobalt-aluminate spinel or cobalt silicate dyes have been reported to exceed the Danish hygienic standard by 1.3- to 172-fold (Tüchsen et al. 1996) (see Section 4). Due to improvements made to workplace conditions in the 1982 to 1992 time period, concentrations of cobalt in workplace air decreased from 1,356 nmol/m³ [80 μg/m³] to 454 nmol/m³ [26 μg/m³] and worker urinary cobalt decreased from 100-fold to 10-fold above median concentration of controls (IARC 1991; 2006). Several studies have been published reporting urine and blood cobalt levels for pottery or plate painters in Denmark and cloisonne workers in Japan (see Table B-2). The mean urine levels were generally elevated, with levels in the 10s of μg/g creatinine for the pottery or plate painters, but <2 μg/L for the glaze workers in cloisonne production. Mean blood levels did not exceed 3 μg/L for any of the studies identified. No cobalt levels in hair or nails were identified for workers in these industries.

U.S. cobalt occupational exposure level data available from NIOSH HETA surveys for chemicals and pigments indicate the following: workplace air levels range from not detected to 21 μg/m³; surface wipe levels range from not detected to 250 μg/100 cm²; and cobalt in bulk samples of work materials ranges from less than 0.01% to 0.03% (Almaguer 1987; Apol 1976; Burr et al. 2005; Chen et al. 2008; Durgam and Aristeguieta 2010; Hall 2003; Kawamoto et al. 1999; Rosensteel et al. 1977; Zey 1985).

2.5.5. Electronics, “Green” Energy, and Recycling of Electronic and Electrical Waste

Recycling can be classified as either informal or formal. Informal e-waste recycling which is dismantling of end-of-life electronics by primitive techniques (e.g., mechanical shredding and open burning) can result in the release of cobalt and other toxic chemicals and generally occurs in developing countries such as China, India, Pakistan, Vietnam, Ghana, and Nigeria (Asante et al. 2012; Grant et al. 2013; Wang et al. 2009). Biomonitoring data from an informal e-waste recycling site in Ghana showed a geometric mean urinary cobalt level of 1.6 μg/L for e-waste recycling workers (Asante et al. 2012). Formal e-waste recycling involves the use of properly designed equipment to safely remove recoverable materials from obsolete electronics while protecting workers and the environment. Personal breathing zone (PBZ), blood, and urinary cobalt have been reported for three formal e-waste recycling sites in Sweden (Julander et al. 2014). PBZ data showed a geometric mean cobalt concentration of 0.066 μg/m³ in the collected inhalable fraction and 0.041 μg/m³ in the total dust fraction. Median blood cobalt reported for two sampling occasions were 0.081 μg/L (first occasion) and 0.073 μg/L (second occasion, significantly higher than in office workers, p ≤ 0.05). Median urinary cobalt reported for two sampling occasions were 0.25 μg/L and 0.21 μg/L.

U.S. cobalt occupational exposure level data available from NIOSH HETA surveys for electronics, “green” energy, and recycling indicate the following: workplace air levels range from not detected to 1.17 μg/m³; the one reported surface wipe level was reported as “detected” (level of detection = 0.02 μg/sample); and the one reported skin (i.e., hand or neck) wipe level was reported as “detected” (level of detection = 0.04 μg/sample) (Beaucham et al. 2014; Thoburn and Larsen 1976).

2.6. Surgical Implants

Patients receiving cobalt-containing surgical implants (e.g., orthopedic joint replacements, spinal system, dental implants, etc.) are potentially exposed to cobalt particles that are released from wear and/or corrosion of the implants. Release of metals from joint replacements (articulating surgical devices) has been characterized the most and lower levels of metals are released from non-articulating surgical devices (such as plates and screws) (Keegan et al. 2008). The total number of hip replacements in the United States has been variously reported as 120,000 per year (Polyzois et al. 2012) or 400,000 per year (Devlin et al. 2013; Frank 2012) with total knee replacements over 600,000 per year (Bernstein and Derman 2014).

Total hip implants consist of (1) femoral head attached to a stem that is inserted in the thigh bone (usually made of ceramic or metal) and (2) a socket or cup that is anchored in the pelvis, which can be made of metal, ceramic or polyethylene. Cobalt-chromium-molybdenum (CoCrMo) alloy is the predominant alloy used in metal-containing implants, e.g., metal on metal (MoM) implants (both articulating surfaces are metal), polyethylene on metal or metal on ceramic implants); other metals such as nickel, tungsten, iron, aluminum, and titanium may also be used in implants. A MoM resurfacing hip prosthesis consists of a femoral head capped with a metal covering. MoM hip implants may release a greater number and smaller particles than other types of implants and their use is declining in the United States (Bradberry et al. 2014; Devlin et al. 2013).

Total knee replacement implants consists of (1) a metallic femoral component that attaches to the end of the femur, (2) a plastic articulating layer, and (3) a tibial component that permanently binds the articulating layer to the top of the tibia (KRC 2015). The most common metal components consist of either cobalt chrome or titanium (Novick 2013). Unlike some hip implants with metal-to-metal contact, knee implants are designed so that metal surfaces do not contact each other.

Blood, serum and urine concentrations of cobalt and chromium generally rise after implantation of MoM hip prosthesis; maximum levels are usually reached in the first year after operation and decline in subsequent years (Bradberry et al. 2014). A review of 43 studies with different MoM bearing found that mean blood levels of cobalt ranged from 0.9 to 3.4 μg/L in patients with well-functioning implants (Jantzen et al. 2013) (see Table B-1 for cobalt levels in blood, serum, urine from studies of hip implant patients and Figure 2-1 and Figure 2-2 for graphs of urine and hair levels). Only one study reported levels in hair following placement of the implants and not studies were identified that reported levels in nails for hip implants; levels in hair 6 months and 12 months after implant were higher in hair from patients with metal-on-metal (53.3 μg/g at 6 months and 47.4 μg/g at 12 months) compared to patients with metal-on-polyethylene hip implants (3.4 μg/g at 6 months and 4.2 μg/g at 12 months). Urine levels identified from studies of hip implants reported as stable or that did not specifically address stability ranged from ~0.7 to 12 μg/L) (see Figure 2-1 and Table B-2 and Table B-3). These differences might be explained by factors such as variations in implant design, differences in patient demographics, or differences in the time elapsed between surgery and sample collection (Schaffer et al. 1999) and a lack of information regarding stability or wear status of the implant.

One in eight total hip implants requires revision within 10 years, and 60% of those are due to wear-related complications (Bradberry et al. 2014). Release of metal (wear debris) from implants results from friction between the bearing surfaces and corrosion from non-moving parts, which is caused by body fluids contacting the metal surfaces or by formation of an electrochemical couple between different metal components (Sampson and Hart 2012). The Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom issued a safety alert that proposed a level of 7 μg/L cobalt in blood as an action level for further clinical investigation and action (MHRA 2012) and 10 μg/L in serum was proposed by the Mayo Clinic in the United States (Mayo Clinic 2015). Dunstan et al. (2005) also reported blood cobalt levels of 19 and 52 μg/L for two individuals with radiologically loose metal-on-metal hip implants. In rare cases, high levels of cobalt from failed implants may be associated with toxicity. A review of literature published since 1950 identified 18 case reports of hip implant patients with cobalt-associated systematic toxicity (such as cardio-, neuro-, or ocular toxicity) and found that the median cobalt blood levels were 506 μg/L; range = 353 to 6,521) among 10 patients with failed ceramic implants and 34.5 μg/L (range = 13.6 to 398.6) among 8 patients with MoM implants (Bradberry et al. 2014). Removal of a joint replacement device that is associated with high cobalt ion levels generally results in decreased cobalt ion levels as reported by Rodriguez de la Flor et al. (2013) for 11 hip implant patients before revision with mean serum cobalt of 25.8 μg/L, which decreased to 12.1 μg/L after revision surgery (see Table B-2). Only one study (Rodriguez de la Flor et al. 2013) was identified that reported mean levels in urine (~205 μg/l) and hair (47.1 μg/g) (see Figure 2-2, and Table B-2) for unstable hip implants and no data were identified for cobalt levels in nails.

2.7. Other Sources of Exposure: Food, Consumer and Other Medical Products and Tobacco

The general public is exposed to cobalt primarily through consumption of food and to a lesser degree through inhalation of ambient air and ingestion of drinking water; average daily cobalt intake from food has been reported to be 11 μg/day (ATSDR 2004; Lison 2015). Although this amount includes cobalt as part of both vitamin B₁₂ and other cobalt compounds (ATSDR 2004), green, leafy vegetables and fresh cereals generally contain the most cobalt (IARC 1991), and these plant sources of cobalt do not contain vitamin B₁₂. No estimate for an average dietary intake of cobalt in the United States was identified. Reported values for cobalt content of foods can vary due to differences in environmental cobalt levels, analytical difficulties, and inadequate analytical techniques.

A past use of cobalt (as cobalt sulfate) was as an additive in some beers (NTP 1998), which was based on a U.S. patent (Thorn and Wrey 1958) for the use of cobaltous nitrate or cobaltous chloride to reduce the tendency for beer to gush or “overfoam” and to increase its foam stability. However, in 1963 to 1964 a form of cardiomyopathy was linked with consumption of beer containing cobalt (Alexander 1969), and in 1966 the FDA prohibited addition of cobaltous compounds to any human food, including beer, in the United States (see Regulations and Guidelines in Part 2, Cancer Hazard Profile).

Higher cobalt intake may result from consumption of over-the-counter or prescription vitamin and mineral preparations (e.g., cobalt chloride). In the 1970s, oral intake of cobalt chloride was used to increase red blood cell counts in anemic patients (but discontinued when enlarged thyroids and goiters were observed at higher doses). In the last decade, oral administration of cobalt chloride has been used to correct excessive estrogen production during female hormone replacement therapy (Lippi et al. 2005; Tvermoes et al. 2013; Unice et al. 2012).

Cobalt is present in consumer products including cleaners, detergents, and soaps (ATSDR 2004). The NLM Household Products Database listed 6 products containing cobalt as an ingredient: 1 nickel metal hydride battery (5% to 10% cobalt), 4 dishwasher detergents (2 powders and 2 semi-solid pouches containing powder), and 1 spray car wax product (HPD 2014).

Different brands of tobacco have been reported to contain cobalt ranging from <0.3 to 2.3 μg/g dry weight; 0.5% of the cobalt content is transferred to mainstream smoke (WHO 2006). Smokers with no occupational exposure have been reported to have a significantly higher mean urinary cobalt concentration (0.6 μg/L, SD = 0.6) than non-smokers (0.3 μg/L, SD = 0.1); cobalt concentrations in blood were the same (Alexandersson 1988; as cited in IARC 1991). However, examination of urinary cobalt levels between cigarette smoke-exposed and unexposed NHANES participants for survey years 1999 to 2004 indicates that there was no significant difference in urinary cobalt levels for smokers and non-smokers (unadjusted for creatinine) (Richter et al. 2009). Richter et al. (2009) noted that while cobalt deficiencies were not reported, smoking does interfere with vitamin B₁₂ absorption.

2.8. Potential for Environmental Exposure

Information on potential for environmental exposure discussed below includes data for releases (Section 2.8.1), occurrence (Section 2.8.2), and exposure (Section 2.8.3).

2.8.1. Releases

Approximately 75,000 metric tons of cobalt enters the global environment annually (CDI 2006; Shedd 1993). Cobalt is released through the natural processes of rock weathering and biological extraction (i.e., biochemical processes of bacteria and other microorganisms that extract cobalt from rocks and soils). Figure 2-3 shows cobalt released from anthropogenic processes (i.e., burning of fossil fuels, metal production and use). Similar amounts come from natural (40,000 metric tons) and anthropogenic (35,000 metric tons) sources; the majority of the natural source contribution is from biochemical processes and the majority of the anthropogenic contribution is from metal production and use.

Figure 2-3

Flow of Cobalt Released from Anthropogenic Processes

Cobalt’s widespread use in numerous commercial, industrial (e.g., mining and extraction from ores), and military applications results in releases to the environment through various waste streams. According to the U.S. EPA Toxics Release Inventory (TRI), total reported on- and offsite release of cobalt and cobalt compounds was approximately 5.5 million pounds from 723 facilities in 2013 (USEPA 2014a; 2014b; 2014c). Calculations based on media-specific release data from TRI indicate that releases to land accounted for 82% of total releases, offsite disposal for 15%, and underground injection, air, and water for 1% each in 2013. The scenarios that generally contribute most to U.S. releases of cobalt and cobalt compounds as reported to EPA (USEPA 2014d) include gold, copper, and nickel ore mining, hazardous waste treatment and disposal, non-ferrous metal smelting and refining, fossil fuel electric power generation, and chemical operations (e.g., petrochemical manufacturing and synthetic dye and pigment manufacturing). Recycling of e-waste can result in releases to the environment (particularly from informal e-waste recycling; see Section 2.5.5). Other potential exposure scenarios (e.g., copper smelting) exist, but no air data were identified.

2.8.2. Occurrence

The average concentration of cobalt in ambient air in the United States has been reported to be approximately 0.4 ng/m³ (ATSDR 2004). Levels can be orders of magnitude higher near source areas (e.g., near facilities processing cobalt-containing alloys, compounds, etc.). Sources of cobalt in the atmosphere can be natural (e.g., wind-blown continental dust, seawater spray, volcanoes, forest fires, and marine biogenic emissions), and anthropogenic (e.g., burning of fossil fuels, mining and smelting of cobalt-containing ores, hazardous waste treatment and disposal, etc.) (ATSDR 2004; USEPA 2012; 2014a)).

Median cobalt concentration in U.S. drinking water has been reported to be <2.0 μg/L; however, levels as high as 107 μg/L have been reported. It is unclear whether higher levels could indicate cobalt being picked up in distribution systems (ATSDR 2004). Cobalt concentrations have been reported to range from 0.01 to 4 μg/L in seawater and from 0.1 to 10 μg/L in freshwater and groundwater (IARC 2006).

Studies have reported cobalt soil concentrations ranging from 0.1 to 50 ppm. However, soils near ore deposits, phosphate rock, ore smelting facilities, soils contaminated by airport or highway traffic, or other source areas may contain higher concentrations (e.g., soil cobalt concentrations as high as 12,700 ppm reported near hard-metal facilities) (IARC 2006). The soil concentration of cobalt available to be taken up by plants has been reported to range from 0.1 to 2 ppm (IARC 2006).

2.8.3. Exposure

Information on exposures to cobalt from environmental releases is limited, and no data for U.S. exposures were identified. Biomonitoring research has confirmed general public exposure to cobalt in scenarios including non-ferrous metal mining (see Figure 2-1). A study of metal exposure from mining and processing of non-ferrous metals in Katanga, Democratic Republic of Congo found that geometric mean urinary cobalt concentrations were 4.5-fold higher for adults and 6.6-fold higher for children in urban and rural communities near mines and metal smelters than in rural communities without mining or industrial activities (Cheyns et al. 2014).

2.9. Summary and Synthesis

Several lines of evidence indicate that a significant number of people living in the United States are exposed to cobalt and cobalt compounds. This evidence includes cobalt and several cobalt compounds being high-production-volume chemicals, widespread use in numerous commercial, industrial, and military applications, and biological monitoring data (i.e., urine, blood, hair, and nails) demonstrating exposure in occupationally and non-occupationally exposed populations. TRI data indicate that production- and use-related releases of cobalt and cobalt compounds have occurred at numerous industrial facilities in the United States.

Biomonitoring studies measuring cobalt in the urine of people exposed to cobalt from different sources indicate that the highest levels were generally seen for occupational exposures and unstable hip implants; lower cobalt levels were due to exposure from stable hip implants or the environment, or in the general public (source of exposure unknown). In general, levels of cobalt in blood (including whole blood, plasma, and serum), in hair, and in nails show a similar pattern to those for urinary cobalt levels.

The primary route of occupational exposure to cobalt is via inhalation of dust, fumes, mists containing cobalt, or gaseous cobalt carbonyl. Dermal contact with hard metal and cobalt salts can result in systemic uptake. Occupational exposure to cobalt occurs during (1) the refining of cobalt, (2) the production of cobalt powders, (3) use in the hard metal, diamond tool, and alloy industries (including the production and use of these cobalt-containing products), use to make chemicals, pigments, and electronics, and (4) in the recycling of electronics (more of a global than U.S. concern). Workers regenerating spent catalysts may also be exposed to cobalt sulfides. Occupational exposure has been documented by measurements of cobalt in ambient workplace air, worker blood and urine, and deceased worker lung tissue. U.S. occupational exposure data are available for the following industries: metallurgical; cemented carbides and bonded diamonds; chemicals and pigments; and electronics, “green” energy, and recycling.

Some of the highest levels of cobalt reported in blood or urine have been associated with failed medical devices (such as metallic hip implants containing cobalt alloys). Levels of cobalt reported in blood or urine from stable hip implants are lower than those reported for unstable hip implants and occupational exposures but higher than those reported for exposures from the environment or in the general public.

Although exposure to cobalt in the general public can occur via inhalation of ambient air and ingestion of drinking water, however, food has been reported to be the largest source of cobalt exposure to the general public. Higher cobalt intake may result from consumption of over-the-counter or prescription mineral preparations. Other sources of exposure to cobalt and cobalt compounds include some household consumer products, primarily dishwasher detergents and nickel metal hydride batteries.

This is a work of the US government and distributed under the terms of the Public Domain

Bookshelf ID: NBK580288

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