Cadmium and Certain Cadmium Compounds Reasonably Anticipated to be a Human Carcinogen - Eighth Report on Carcinogens 

CARCINOGENICITY

There is sufficient evidence for the carcinogenicity of cadmium (Cd) (CAS No. 7440-43-9) and the following cadmium compounds in experimental animals: cadmium chloride (10108-64-2), cadmium oxide (1306-19-0), cadmium sulfate (10124-36-4), and cadmium sulfide (1306-23-6) (IARC V.2, 1973; IARC V.11, 1976; IARC S.4, 1982; IARC S.7, 1987; ATSDR, 1993d). An IARC Working Group did not evaluate the carcinogenicity of cadmium carbonate (513-78-0), cadmium fluoborate (14486-19-2), or cadmium nitrate (10325-94-7). When administered by intramuscular injection, cadmium powder induced rhabdomyosarcomas and some fibrosarcomas in female rats. When administered by subcutaneous or intramuscular injection, cadmium sulfide induced local sarcomas in rats of both sexes. When administered by subcutaneous injection, cadmium sulfate induced local sarcomas and interstitial cell tumors of the testis in rats. When administered by subcutaneous injection, cadmium chloride induced interstitial cell tumors of the testis in rats, sarcomas and spindle cell sarcomas in male rats, and interstitial cell tumors of the testis in mice. When administered by injection into the ventral prostate, cadmium chloride induced a low incidence of prostatic carcinomas in rats. Male rats exposed continuously to cadmium chloride aerosols developed dose-related increases in adenocarcinomas, epidermoid (squamous cell) carcinomas, combined epidermoid carcinomas and adenocarcinomas, and mucoepidermoid carcinomas of the lung (Takenaka et al., 1983). When administered by subcutaneous injection, cadmium oxide induced local tumors in female rats (IARC V.11, 1976). When administered by intratracheal instillation, cadmium oxide induced an increased incidence of mammary tumors and an increase in tumors at multiple sites in male rats (ATSDR, 1993d).

An IARC Working Group reported that there is limited evidence for the carcinogenicity of cadmium and certain cadmium compounds in humans (IARC S.4, 1982; IARC S.7, 1987). Studies have suggested that human exposure to cadmium (primarily as the oxide) is associated with increased risks of prostatic, respiratory, and genitourinary cancers (IARC V.2, 1973; IARC V.11, 1976; IARC S.4, 1982; IARC S.7, 1987; ATSDR, 1993d). In one follow-up study of an investigation of cadmium-nickel battery workers and cadmium-copper alloy factory workers, additional cases of nasopharyngeal, colorectal, prostatic, and lung cancer were reported. In another study, the mortality of cadmium-copper alloy workers who were exposed to cadmium fume was compared with that of workers exposed indirectly to cadmium but also to arsenic. A third group of iron or brass founders was included, and the mortality rates were compared separately with statistics for the general population. Significantly increased mortality from prostatic, genitourinary and lung cancers was seen for people working in the vicinity but not for the cadmium workers themselves. In follow-up studies of four populations of cadmium-exposed workers, excess lung cancer was noted among male workers employed at 1 of 17 plants in a group that had had "ever medium" exposure for 10 years or more; an excess risk of prostatic cancer was seen in a group that had had "always low" exposures for 10 years or more. In a follow-up study of cadmium smelter workers, a significant trend was noted for cumulative cadmium exposure and lung cancer mortality. Potential confounding factors in these studies, such as smoking and exposure to nickel and arsenic, do not appear to account for the excess of lung cancer deaths.

PROPERTIES

Cadmium occurs as a soft, blue-white, malleable metal or grayish-white powder. It is soluble in acid, ammonium nitrate, and hot sulfuric acid and insoluble in cold and hot water. Cadmium carbonate occurs as a white amorphous powder that is soluble in acids, potassium cyanate, and ammonium salts and insoluble in ammonia and water, both cold and hot. Cadmium chloride occurs as small, white-to-colorless, hexagonal crystals. It is soluble in water and acetone and insoluble in ethanol. Cadmium fluoborate is extremely hygroscopic and very soluble in water. When heated to decomposition, it emits toxic fumes of cadmium, hydrofluoric acid, and other fluorinated compounds. Cadmium nitrate occurs as white, amorphous pieces or hygroscopic needles. It is very soluble in acids and soluble in ethanol, acetone, water, and ammonia. Cadmium oxide occurs as a colorless amorphous powder or brown-red cubic crystals. It is soluble in acids, ammonium salts, and alkalies, but is insoluble in cold and hot water. When heated to decomposition, it emits toxic fumes of cadmium. Cadmium sulfate occurs as white rhombic crystals. It is soluble in water but insoluble in alcohol, acetate, and ammonia. Cadmium sulfide is a yellow-orange or brown powder. It forms a colloid in hot water; it is soluble in acids and ammonia and insoluble in cold water. When heated to decomposition, cadmium sulfate and cadmium sulfide emit toxic fumes of cadmium and sulfur oxides (SO_x).

Cadmium metal is available in purities ranging from 99.5%-99.999% in the following grades: technical, powder, pure sticks, ingots, slabs, and high-purity crystals with less than 10 ppm impurities. Cadmium carbonate is available in a commercial grade which has a purity of about 98% with lead, zinc, and iron as impurities. Reagent-grade cadmium carbonate, with purities ranging from 99.9%-99.995%, is also available. Commercial cadmium chloride is a mixture of hydrates that is similar to the dihydrate form of cadmium chloride. The commercial grade available in the United States typically contains about 51% cadmium and 0.005% each of iron and copper; higher purity grades (99.9%) are also available. Cadmium fluoborate is available commercially in a 50% aqueous solution. Cadmium nitrate is available in technical and reagent grades (purity > 99%) with typical impurities of chloride, sulfate, copper, iron, lead, zinc, and arsenic. Commercial-grade cadmium oxide is available in the United States with a purity of 99.7%; common contaminants are lead and thallium. Cadmium sulfate is available in technical and C.P. grades. Cadmium sulfide is available in technical, N.D., high-purity (single crystals), and commercial grades. Typically, cadmium sulfide is available in mixtures depending upon its use as either a pigment or a phosphor.

USE

In 1989, batteries (34%) were the primary market for cadmium, followed by coating and plating (27%), pigments (15%), plastic and synthetic products (14%), and alloys and miscellaneous uses (10%) (USDOI, 1990). In 1988, the use of cadmium in batteries surpassed coating and plating operations. The estimated consumption pattern for cadmium in 1987 was coating and plating, 30%; batteries, 30%; pigments, 20%; plastics and synthetic products, 15%; and alloys and other uses, 5% (USDOI, 1988). Cadmium (elemental) is used primarily as an electroplated coating on fabricated steel and cast iron parts for corrosion protection. It is also used in bearing, brazing, and low-melting alloys, in nickel-cadmium storage batteries, reactor control rods, and as a hardener for copper. The intermetallic compounds, including cadmium sulfide (CdS), cadmium selenide (CdSe), and cadmium telluride (CdTe), have been used as semiconductors for photoconductors, photovoltaic cells, and infrared windows (ACGIHa, 1986; Kirk-Othmer V.4, 1978). Cadmium carbonate is used as a catalyst in organic reactions and as a source of cadmium in other reactions. Cadmium chloride is used in photocopying, printing, dyeing, electroplating baths, and the manufacture of special mirrors and of cadmium yellow. A cadmium fluoborate bath is used for electrodeposition of cadmium on high-strength steels to avoid the problem of hydrogen embrittlement inherent in cyanide plating (Kirk-Othmer V.4, 1978). Cadmium nitrate and cadmium oxide are used in the production of cadmium salts, photographic emulsions, coloring glass and porcelain, and in the laboratory as reagents. Cadmium oxide also finds use in plating baths, in electrodes for storage batteries, in phosphors, as a nematocide, as a starting material for poly(vinyl chloride) (PVC) heat stabilizers, and as an additive in nitrite rubbers and plastics such as Teflon^®. Cadmium sulfate and cadmium sulfide are used in pigments, fluorescent screens, in photoelectric cells, and in electroplating. Cadmium sulfide is the most widely used cadmium compound and is used primarily as a pigment (Sax, 1987; Kirk-Othmer V.4, 1976).

PRODUCTION

Cadmium is recovered as a by-product of smelting domestic and imported zinc concentrates; as such, its production is dependent upon the demand for zinc. In 1989, four U.S. companies produced an estimated 3.9 million lb of cadmium (USDOI, 1990). Estimated U.S. cadmium imports almost reached 6 million lb in 1989. Estimated U.S. cadmium exports exceeded 1 million lb in 1989. Approximately 4.2 million lb of cadmium were produced domestically in 1988. U.S. imports for that year were almost 5.5 million lb. U.S. cadmium exports were nearly 1.4 million lb in 1988. In 1987, it was estimated that four companies produced 3.3 million lb of cadmium. Also in 1987, 6.6 million lb of cadmium metal were imported and 396,000 lb of cadmium were exported. Nearly 3.3 million lb of cadmium were produced in 1986, 7.0 million lb of cadmium metal were imported, and 83,600 lb of cadmium were exported. In 1985, 3.5 million lb of cadmium were produced, 4.4 million lb of cadmium metal were imported, and 189,200 lb of cadmium were exported. Production of cadmium in 1984 was 3.7 million lb, imports of cadmium metal were 4.2 million lb, and exports of cadmium were 233,200 lb. In 1983, 2.3 million lb of cadmium were produced domestically, 4.8 million lb of cadmium metal were imported, and 374,000 lb of cadmium were exported (USDOI, 1988; USDOI, 1987). In 1982, 2.2 million lb of cadmium were produced, 5.1 million lb of cadmium metal and 24,200 lb of cadmium flue dust were imported, and 24,200 lb of cadmium were exported. More than 3.5 million lb of cadmium were produced in 1981, 6.8 million lb of cadmium metal were imported, and 525,800 lb of cadmium were exported. In 1980, 3.5 million lb of cadmium were produced, 5.8 million lb of cadmium metal were imported, and 519,200 lb of cadmium were exported (USDOI, 1985). The 1979 TSCA Inventory reported that in 1977, there were 14 producers of cadmium producing 6.3 million lb and 18 importers importing 2.6 million lb (TSCA, 1979). Production for 1972 through 1977 ranged from 7.5 million to 4.1 million lb (Kirk-Othmer V.4, 1978).

The 1979 TSCA Inventory identified nine producers of cadmium carbonate refining 116,500 lb and two companies importing 1,000 lb in 1977. The TSCA Inventory also reported that in 1977, 116,000 lb of cadmium chloride were manufactured by eight producers and 2,000 lb were imported by two firms; four companies produced 5,500 lb of cadmium fluoborate; 561,000 lb of cadmium nitrate were produced by eight firms and 500 lb were imported by one company; 15.0 million lb of cadmium oxide were produced by 12 companies and 2,000 lb imported by four companies; 1.3 million lb of cadmium sulfate were manufactured by 14 producers and 1,000 lb were imported by three firms; and 12 firms produced 1.1 million lb of cadmium sulfide and nine companies imported 724,000 lb, with some site limitations. The CBI Aggregate was less than 1 million lb each for cadmium carbonate, cadmium chloride and cadmium fluoborate; and between 1 million and 100 million lb each for cadmium nitrate, cadmium oxide, cadmium sulfate and cadmium sulfide (TSCA, 1979).

EXPOSURE

The primary routes of potential human exposure to cadmium and certain cadmium compounds are inhalation, dermal contact, and ingestion. The four major sources of occupational exposure are smelting of zinc and lead ores; producing, processing, and handling of cadmium powders; welding or remelting of cadmium-coated steel; and working with solders that contain cadmium (ATSDR, 1993d; NIOSH 42, 1984). The major route of occupational exposure to cadmium is inhalation. An estimated 213,000 workers were exposed to cadmium in the workplace at levels equal to or greater than 1 µg/m³ (OSHA, 1987). Of these 213,000 workers, 65% were exposed to concentrations between 1 µg/m³ and 39 µg/m³; 21% were exposed to cadmium at concentrations between 40 µg/m³ and 99 µg/m³; and 14% were exposed to cadmium concentrations greater than 100 µg/m³. The National Occupational Hazard Survey, conducted by NIOSH from 1972 to 1974, estimated that approximately 1.5 million workers were possibly exposed to cadmium, of which 100,000 were identified with exposure to specific cadmium compounds or with industries that utilize cadmium (NIOSH, 1976). The National Occupational Exposure Survey (1981-1983) estimated that a total of 69,100 workers, including 15,400 women, potentially were exposed to cadmium compounds including cadmium, cadmium chloride, cadmium sulfate, cadmium nitrate, cadmium oxide, cadmium sulfide, and cadmium fluoborate (NIOSH, 1984).

Consumer exposure occurs through inhalation and ingestion. Small quantities of cadmium appear in the air, water, and soil. Food is the main source of human exposure (Merian, 1984; Nordberg et al., 1985). There is significant inhalation exposure in industrial areas where zinc, lead, or copper smelters are located. Ambient air concentrations in rural areas are usually less than 1 ng/m³, and in industrial areas range from 5-40 ng/m³. (ATSDR, 1993d). In the United States, about 2 million lb of cadmium are emitted during cadmium production and up to another 2 million lb are emitted from the use of cadmium (Merian, 1984). Cadmium is highly volatile and about two thirds of the cadmium produced is dissipated into the environment (Merian, 1984). Industry has increased cadmium recovery at primary smelters; release to the environment from industrial operations is expected to decrease (USDOI, 1990). The Toxic Chemical Release Inventory (EPA) listed 78 industrial facilities that produced, processed, or otherwise used cadmium in 1988 (TRI, 1990). In compliance with the Community Right-to-Know Program, the facilities reported releases of cadmium to the environment which were estimated to total 668,000 lb in 1988. Burning of fossil fuels, such as coal or oil, and the incineration of municipal waste materials contributes to the cadmium emitted in the air (ATSDR, 1993d; Merian, 1984). In the United States, up to 2 million lb of cadmium annually are polluting the air from coal and fossil fuel burning. Atmospheric cadmium is mainly in the forms of cadmium oxide and cadmium chloride (Merian, 1984). Smoking may double an individual's intake of cadmium; tobacco smokers are exposed to an estimated 1.7µg Cd/cigarette (IARC V.11, 1976; ATSDR, 1993d). Drinking water concentrations of cadmium have been estimated to be < 1 µg/l. Cadmium can leach into ground water from pipes and solder used on pipes or from chemical/hazardous waste sites. It has been estimated that the ground water in New Jersey has a median level of 1µg Cd/l with a high level of 405 µg/l (ATSDR, 1993d). Nickel-cadmium batteries used in electronic equipment are primary sources of cadmium in municipal trash and garbage (Pollut. Eng., 1989). Cadmium released in solid waste totaled 542,000 lb in 1988. Contaminated topsoil may be indirectly responsible for the greatest human exposure to cadmium due to the uptake of cadmium in soil into edible plants and tobacco. Topsoil may be contaminated by the application of phosphate fertilizers or sewage sludge. It has been found that uncontaminated top soil in the Unites States may contain an average of 0.25 ppm cadmium (ATSDR, 1993d; Merian, 1984). Potential daily intake is 10-20 &g and may be assumed to increase in the future (Piscator, 1985). A decrease in soil pH due to acidic precipitation may increase dietary cadmium. CPSC has investigated the consumer hazard posed by inks used in printed products and by the products themselves but found no cadmium in the inks or in the final consumer products.

REGULATIONS

Under the Clean Water Act (CWA), the water quality criteria published by EPA for cadmium and its compounds for the protection of human health are identical to Safe Drinking Water Act (SDWA) standards of 10µg/l. EPA's Carcinogen Assessment Group includes cadmium oxide, cadmium sulfide, and cadmium sulfate on its list of potential carcinogens. Under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), reportable quantities (RQs) have been established for cadmium and cadmium chloride. EPA issued a Rebuttable Presumption Against Registration (RPAR) for cadmium-containing pesticides under FIFRA. Also under FIFRA, there are labeling and reporting requirements. Under the Food, Drug, and Cosmetic Act (FD&CA), cadmium compounds are regulated as toxic inert ingredients in pesticides. Cadmium and cadmium compounds are also regulated under the Resource Conservation and Recovery Act (RCRA) and Superfund Amendments and Reauthorization Act (SARA). Both RCRA and SARA subject cadmium and its compounds to reporting requirements. FDA, under FD&CA, has set a maximum concentration level of 0.005 mg Cd/L in bottled water and limits the amount of cadmium in color additives and direct food additives. In 1984, NIOSH recommended that exposure to cadmium be reduced to the lowest possible level (NIOSHc, 1996). OSHA adopted permissible exposure limits (PELs) for toxic effects other than cancer for cadmium: 0.1 mg/m³ as an 8-hr time-weighted average (TWA) for fumes, 0.3 mg/m³ as a ceiling for fumes, 0.2 mg/m³ as an 8-hr TWA for dust, and 0.6 mg/m³ as a ceiling for dust; the standards were adopted by OSHA. OSHA regulates cadmium and certain cadmium compounds under the Hazard Communication Standard and as chemical hazards in laboratories.

source: http://ntp-server.niehs.nih.gov/htdocs/8_RoC/RAC/Cadmium&cmpds.html