Cadmium
Cadmium is a chemical element with the symbol Cd and atomic number 48.[1] It is a soft, silvery-white transition metal in group 12 of the periodic table, chemically resembling zinc and mercury, with a low melting point of 321 °C and density of 8.65 g/cm³.[2] Cadmium was discovered in 1817 by German chemist Friedrich Stromeyer, who isolated it from an impurity in zinc carbonate that produced a yellow precipitate.[3] In nature, cadmium rarely occurs in concentrated deposits but is present at concentrations of 0.1–0.5% in zinc ores like sphalerite, from which it is extracted almost entirely as a byproduct of zinc refining processes.[4][1] Key industrial applications of cadmium include its use as the active cathode material in nickel-cadmium rechargeable batteries, which provide high energy density and reliability; production of cadmium sulfide and selenide pigments yielding brilliant yellow, orange, and red hues resistant to fading; and electrodeposition for corrosion-resistant coatings on steel components.[5] Despite these utilities, cadmium's extreme toxicity—manifesting as renal dysfunction, bone demineralization (Itai-itai disease in severe cases), carcinogenicity, and bioaccumulation in food chains—has prompted global regulatory restrictions, phasing out non-essential uses and emphasizing recycling from end-of-life products to mitigate environmental release.[6][7]Physical and Chemical Properties
Physical properties
Cadmium is a soft, malleable, and ductile metal with a silvery-white appearance and a faint bluish tinge.[8][2] It can be easily cut with a knife due to its low hardness, with Vickers hardness values ranging from 68.5 to 73.5 under a 10 g load.[9] At 20 °C and standard pressure, cadmium has a density of 8.65 g/cm³.[10] It melts at 321.07 °C and boils at 767 °C.[2] Cadmium adopts a hexagonal close-packed crystal structure at room temperature, with lattice constants a = 0.297 nm and c = 0.561 nm.[10] Cadmium exhibits moderate thermal conductivity of 97 W·m⁻¹·K⁻¹ and a coefficient of linear thermal expansion of 30.8 × 10⁻⁶ K⁻¹.[11] Its electrical resistivity is 72.7 nΩ·m at 22 °C, corresponding to an electrical conductivity of approximately 1.4 × 10⁷ S/m.[11] Cadmium is diamagnetic and shows no magnetic ordering at room temperature.[9] The following table summarizes select physical properties of elemental cadmium:| Property | Value | Conditions |
|---|---|---|
| Density | 8.65 g/cm³ | 20 °C |
| Melting point | 321.07 °C | Standard pressure |
| Boiling point | 767 °C | Standard pressure |
| Thermal conductivity | 97 W·m⁻¹·K⁻¹ | 25 °C |
| Electrical resistivity | 72.7 nΩ·m | 22 °C |
| Coefficient of linear thermal expansion | 30.8 × 10⁻⁶ K⁻¹ | 25 °C |
Chemical properties
Cadmium possesses the electron configuration [Kr] 4d¹⁰ 5s², consistent with its position as a group 12 element.[12] It exhibits a standard electrode potential of -0.402 V and primarily adopts the +2 oxidation state in compounds, forming the Cd²⁺ ion, though rare +1 states occur in specific organocadmium species.[12] [13] The metal shows low reactivity under standard conditions, remaining stable in dry air but developing a superficial oxide layer upon exposure to moist air or heating to 300 °C, where it forms cadmium(II) oxide (CdO) via the reaction 2 Cd(s) + O₂(g) → 2 CdO(s).[14] Cadmium burns in air above the sublimation temperature of CdO (1385 °C), producing the oxide.[14] It reacts slowly with distilled water over 24–48 hours and with steam above 400 °C to yield CdO and hydrogen.[14] The metal dissolves readily in dilute acids such as HCl, liberating hydrogen and forming soluble salts, as in Cd(s) + 2 HCl(aq) → CdCl₂(aq) + H₂(g).[14] Cadmium reacts with halogens to produce dihalides: for example, Cd(s) + F₂(g) → CdF₂(s) (white solid) or Cd(s) + Cl₂(g) → CdCl₂(s).[14] It also forms chalcogenides like cadmium sulfide (CdS, yellow pigment, insoluble in water) upon treatment with H₂S, and similarly CdSe or CdTe with selenium or tellurium.[14] [13] Common compounds include cadmium oxide (CdO, used as a catalyst), cadmium sulfate (CdSO₄, for electroplating), and cadmium hydroxide (Cd(OH)₂, in batteries); most are sparingly soluble in water, with Cd²⁺ showing strong adsorption to organic matter in soils.[13] [12] Cadmium forms tetrahedral complexes, such as [Cd(NH₃)₄]²⁺ with ammonia, reflecting its coordination chemistry akin to zinc.[14]Isotopes and nuclear characteristics
Cadmium has eight isotopes that occur naturally, with mass numbers 106, 108, 110, 111, 112, 113, 114, and 116; these constitute 100% of terrestrial cadmium and are effectively stable, contributing to the element's standard atomic weight of 112.414(4).[15] Their isotopic abundances and relative atomic masses, as determined by mass spectrometry, vary slightly due to geological processes but follow the values in the table below.| Isotope | Relative atomic mass | Isotopic abundance (atom %) |
|---|---|---|
| ^{106}Cd | 105.9064599(12) | 0.0125(6) |
| ^{108}Cd | 107.9041834(12) | 0.0089(3) |
| ^{110}Cd | 109.90300661(61) | 0.1249(18) |
| ^{111}Cd | 110.90418287(61) | 0.1280(12) |
| ^{112}Cd | 111.90276287(60) | 0.2413(21) |
| ^{113}Cd | 112.90440813(45) | 0.1222(12) |
| ^{114}Cd | 113.90336509(43) | 0.2873(42) |
| ^{116}Cd | 115.90476315(17) | 0.0749(18) |
Historical Development
Discovery and initial characterization
Cadmium was discovered in 1817 by Friedrich Stromeyer, a German chemist and professor at the University of Göttingen, during an inspection of pharmaceutical supplies.[4] [20] He examined samples of zinc carbonate (calamine) from two apothecaries in Hanover that failed to conform to standards, noting that upon calcination, they produced a yellow oxide rather than the expected white zinc oxide.[4] [21] Through repeated dissolution, precipitation, and distillation, Stromeyer isolated a new metallic substance from the impurity, which he named cadmium after cadmia fornacum, the ancient term for zinc ore.[4] [20] In the same year, Karl Samuel Leberecht Hermann independently identified the element while analyzing zinc oxide from pharmacies near Glauchau, Germany, confirming its presence as an impurity in zinc compounds.[4] [1] Stromeyer produced the pure metal by reducing cadmium oxide with hydrogen gas, describing it as a soft, ductile, bluish-white solid resembling tin but more malleable and with a lower melting point.[20] Initial chemical tests revealed that cadmium formed a brown oxide distinct from zinc oxide and exhibited solubility behaviors and spectral lines that differentiated it from known metals like zinc, mercury, and tin.[21] [1] Early characterizations included observations of its density around 8.6 g/cm³ and its tendency to tarnish in moist air, forming a protective oxide layer.[4] Stromeyer also noted cadmium's compounds, such as cadmium sulfide, produced vibrant yellow pigments, which contrasted with the white compounds of zinc and hinted at its potential industrial value despite its toxicity not being recognized at the time.[21] These findings established cadmium as a distinct element in the periodic table precursors, with atomic weight estimates aligning it between zinc and mercury.[20]Expansion of industrial applications
The primary early industrial application of cadmium emerged in the form of pigments, with cadmium sulfide (CdS) developed as a brilliant yellow colorant shortly after the element's discovery, entering limited production around 1820 despite initial metal scarcity that constrained output.[22] Cadmium selenide variants extended the palette to vivid reds and oranges by the mid-19th century, prized for their lightfastness and opacity in artists' oils and industrial paints, though total usage remained modest due to high costs and alternative pigments like chrome yellow.[23] Industrial-scale cadmium production began in the 1930s and accelerated through the 1940s, driven by zinc smelting byproducts and enabling broader applications beyond pigments, which had dominated prior demand.[21] This expansion coincided with cadmium electroplating's adoption in the early 1900s for corrosion-resistant coatings on steel components, particularly in aerospace and military hardware where its sacrificial protection outperformed zinc in salt-laden environments; by World War II, it coated aircraft fasteners, bolts, and landing gear, consuming a significant share of output.[24] Rechargeable nickel-cadmium (NiCd) batteries, invented in 1899 by Swedish engineer Waldemar Jungner using cadmium as the negative electrode, saw initial commercialization in Sweden by 1910 but achieved widespread industrial viability only after 1930s production scaling, powering portable devices, emergency lighting, and aviation backups by the mid-20th century.[25] Usage grew from niche to about 8% of global cadmium consumption by 1970, reflecting demand for their high discharge rates and durability despite toxicity concerns.[5] By the 1940s, cadmium's versatility extended to low-melting alloys for solders and fusible links, as well as stabilizers in polyvinyl chloride (PVC) plastics to prevent degradation from heat and light, applications that proliferated post-war in electrical insulation and piping.[21] These developments marked a shift from artisanal pigments to mass-engineered uses, with annual global production rising from under 1,000 metric tons pre-1930 to over 10,000 by the 1960s, though environmental regulations later curbed growth in some sectors.[26]Natural Occurrence and Commercial Production
Geological occurrence and sources
Cadmium is present in the Earth's crust at an average abundance of 0.16 grams per metric ton, ranking 63rd among the elements in crustal concentration.[4] It does not occur in native metallic form and is almost exclusively found in association with other minerals, primarily substituting for zinc in sulfide ores due to their chemical similarity and ionic radius compatibility. The element's geochemical behavior favors incorporation into sphalerite (ZnS), the dominant zinc mineral in hydrothermal and sedimentary deposits, where cadmium substitutes lattice positions up to several percent by weight.[27] The primary cadmium-bearing mineral is greenockite (CdS), a rare cadmium sulfide that typically forms as yellow to reddish coatings or hemimorphic crystals on sphalerite in low-temperature hydrothermal veins or oxidation zones.[2] Other cadmium minerals, such as otavite (CdCO3) and monteponite (CdO), are even less common and occur mainly as secondary alteration products in oxidized environments.[4] Sphalerite from zinc-lead deposits often contains 0.1% to 0.3% cadmium by weight, with higher concentrations (up to 0.4% or more) in Mississippi Valley-type (MVT) and sedimentary-exhalative deposits due to fluid chemistry favoring cadmium enrichment during mineralization.[28] [29] Cadmium is less abundant in primary lead ores like galena (PbS), typically at trace levels (<0.01%), and in copper sulfides, reflecting weaker partitioning into those lattices.[4] Elevated cadmium levels beyond sphalerite associations appear in certain sedimentary rocks, including black shales, phosphorites, and marlstones, where concentrations can exceed crustal averages by factors of 10–100 due to organic matter scavenging or phosphate adsorption during deposition.[30] Volcanic emissions and submarine hydrothermal activity contribute cadmium to ocean sediments, but terrestrial sources dominate geological reservoirs, with zinc ore districts (e.g., those in Australia, China, and Mexico) hosting the bulk of economically viable deposits.[4] Natural mobilization occurs via weathering of these ores, releasing cadmium into soils and waters at rates governed by pH, redox conditions, and microbial activity.[30]Primary production processes
Cadmium is primarily recovered as a byproduct during the hydrometallurgical refining of zinc sulfide ores, such as sphalerite, which typically contain 0.3% to 1.2% cadmium by weight in the concentrate.[31] The process begins with mining and beneficiation of zinc ores, where the ore is crushed, ground, and subjected to froth flotation to produce a zinc sulfide concentrate.[32] This concentrate is then roasted in air to convert zinc sulfide to zinc oxide, followed by leaching with sulfuric acid to form a zinc sulfate solution containing dissolved cadmium ions.[31] In the purification stage of electrolytic zinc production, cadmium is selectively removed from the zinc electrolyte through cementation using zinc dust, which precipitates cadmium as a metallic sponge via the displacement reaction: Cd²⁺ + Zn → Cd + Zn²⁺.[32] The resulting cadmium-zinc sponge is filtered, washed, and further processed—typically by distillation under vacuum or electrolytic refining—to yield high-purity cadmium metal (99.95% or greater).[31] Approximately 3 kilograms of cadmium are associated with each metric ton of zinc processed in primary smelters, accounting for over 80% of global cadmium output.[33] Smaller quantities of cadmium arise from the smelting of lead and copper sulfide ores, where it reports to zinc-rich residues or slags and is recovered similarly via leaching and cementation.[31] Direct mining of cadmium-specific ores, such as greenockite (CdS), is negligible due to their rarity and low concentrations, with nearly all commercial production tied to zinc operations.[32] Global primary cadmium production was around 24,000 metric tons in 2020, predominantly from facilities in China, South Korea, and Japan processing imported zinc concentrates.[33]Secondary production and recycling
Secondary production of cadmium encompasses the recovery of the metal from recycled scrap and waste materials, with spent nickel-cadmium (NiCd) batteries serving as the predominant source, alongside copper-cadmium alloy scrap, complex nonferrous alloys, electric-arc-furnace (EAF) dust, and cadmium telluride (CdTe) solar panels.[34][35] In the United States, dedicated facilities handle secondary recovery, including an Ohio-based operation processing NiCd batteries and a North Carolina facility treating EAF dust generated during steel recycling.[35] Globally, NiCd battery recycling contributes significantly to secondary output, partially compensating for fluctuations in primary production derived from zinc processing.[35] Key recycling methods include pyrometallurgical processes, such as thermal oxidation of battery scrap followed by distillation to volatilize and condense cadmium into high-purity ingots (>99.95% Cd), and hydrometallurgical approaches involving acid dissolution of materials with subsequent precipitation or ion exchange for separation.[36] Pretreatment steps, like crushing, sorting, and magnetic separation, precede these to concentrate cadmium-bearing fractions.[36] In 2000, U.S. consumption of recycled cadmium old scrap totaled 285 metric tons, mainly from NiCd batteries and galvanized steel flue dust, achieving a 15% recycling rate from an estimated 2,400 metric tons generated.[36] Contemporary U.S. secondary production figures are withheld to safeguard proprietary data, though trends indicate sustained reliance on battery scrap amid declining NiCd use due to regulatory restrictions favoring substitutes like lithium-ion batteries.[34][35] Future secondary supplies may expand from end-of-life CdTe photovoltaics as their deployment grows.[34]Industrial and Technological Applications
Corrosion-resistant coatings and electroplating
Cadmium electroplating involves the electrodeposition of a thin layer of cadmium metal onto substrates such as steel, iron, or aluminum to provide sacrificial corrosion protection. The coating acts as an anode relative to the base metal, corroding preferentially in the presence of moisture or electrolytes, thereby shielding the underlying material from oxidation and degradation. This process yields a dense, adherent layer with superior resistance to atmospheric corrosion, particularly in marine or acidic environments, outperforming zinc plating in scenarios involving saltwater exposure due to lower corrosion product volume and reduced embrittlement risks on threaded components.[37][38][39] The electroplating process typically employs an acidic or alkaline cyanide-based electrolyte containing cadmium ions, with an electric current driving the reduction and deposition of cadmium onto the cathodically connected workpiece. Post-plating, a chromate conversion coating is often applied to enhance passivation, forming a protective oxide-chromate film that imparts a characteristic golden hue and extends salt spray resistance to over 500 hours for thicknesses around 8-13 micrometers. Typical coating thicknesses range from 5 to 25 micrometers, classified under standards like AMS QQ-P-416 into Type I (as-plated) and Type II (with supplementary chromate treatment), with minimums of 12.7 micrometers for Class 1 (severe service) down to 5.1 micrometers for Class 3 (mild service).[40][41][42] In industrial applications, cadmium coatings are favored for aerospace fasteners, landing gear components, and hydraulic actuators due to their lubricity (low coefficient of friction), galling resistance, and compatibility with fatigue-prone alloys like high-strength steels. The coating's ductility accommodates substrate deformation without cracking, while its solderability and low electrical contact resistance suit connectors and relays in electronics and military hardware. Despite regulatory restrictions stemming from cadmium's toxicity, its use persists in critical sectors where alternatives like zinc-nickel alloys fail to match performance in extreme conditions, as evidenced by ongoing aerospace specifications prioritizing durability over environmental concerns.[43][44][45]Rechargeable batteries
Nickel-cadmium (NiCd) batteries employ cadmium as the active material in the negative electrode (anode), paired with nickel oxide hydroxide in the positive electrode (cathode) and an alkaline potassium hydroxide electrolyte.[46] During discharge, cadmium oxidizes to cadmium hydroxide, while the cathode reduces to nickel hydroxide, enabling reversible electrochemical reactions that support rechargeability.[47] Typical NiCd cells deliver energy densities of 40-60 Wh/kg, with cadmium comprising a significant portion of the electrode mass, often around 10-20% by weight in sealed variants depending on cell design.[48] NiCd batteries exhibit robust performance characteristics, including cycle lives exceeding 1,000 discharges, tolerance to high discharge rates up to 10C, and operational reliability across temperatures from -40°C to 70°C, making them suitable for demanding applications like power tools, emergency lighting, aviation backup systems, and rail signaling where failure could endanger public safety.[49] [50] They also demonstrate low internal resistance and minimal self-discharge rates of 10-15% per month at room temperature, outperforming lead-acid batteries in these metrics.[51] Despite these advantages, NiCd batteries suffer from the "memory effect," where repeated partial discharges can reduce usable capacity unless full cycles are periodically performed, and their energy density lags behind alternatives like lithium-ion systems.[49] Cadmium's toxicity poses significant environmental and health risks, as it bioaccumulates in organisms and persists in ecosystems, prompting strict regulations; for instance, the European Union's Battery Directive (2006/66/EC, amended) bans NiCd in most consumer products since 2006, permitting use only in industrial, medical, or military contexts where no viable substitutes exist.[51] [52] In the United States, the EPA and state programs mandate recycling to recover cadmium, achieving rates up to 27% of battery-derived cadmium by the early 2000s, though global consumption for batteries has declined as nickel-metal hydride (NiMH) and lithium-ion technologies displace them.[53] [54] Historically, rechargeable batteries accounted for 69% of U.S. apparent cadmium consumption in the late 1990s, but market share has contracted due to regulatory pressures and superior alternatives, with NiCd now comprising less than 5% of portable battery sales in regulated markets as of 2020.[55] [56] Ongoing recycling and substitution efforts continue to mitigate cadmium's role, though NiCd persists in niche high-reliability sectors.[57]Pigments, stabilizers, and plastics
Cadmium pigments consist primarily of cadmium sulfoselenides, offering intense yellow, orange, and red colors with superior lightfastness, hiding power, chemical resistance, and heat stability compared to organic alternatives. Cadmium sulfide (CdS) produces pure yellow tones, while cadmium sulfoselenide variants extend to oranges and maroons through selenium incorporation, enabling a spectrum unmatched by many substitutes in opacity and durability. These pigments find application in high-performance coatings, ceramics, glass enamels, and plastics, where they withstand temperatures exceeding 700°C without decomposition or color shift.[58][59] In plastics, cadmium pigments color thermoplastics and thermosetting resins for automotive parts, road markings, and consumer goods, leveraging their thermal endurance during extrusion and molding processes. Their use persists despite toxicity concerns, as replacements often compromise vibrancy or fade resistance; for instance, in powder coatings, cadmium lithopones provide unmatched weatherability for traffic signs and reflectors. Annual global consumption of cadmium for pigments totals around 1,300 metric tons, representing approximately 8% of refined cadmium production as of 2020.[60][61] Cadmium compounds also functioned as heat stabilizers in polyvinyl chloride (PVC) formulations, with cadmium stearates or laurates—typically paired with barium carboxylates—neutralizing HCl released during thermal degradation to maintain clarity and prevent discoloration. These systems excelled in flexible PVC for cables, flooring, and profiles, imparting outstanding initial color retention and outdoor longevity until the early 2000s. Due to cadmium's established carcinogenicity via inhalation and ingestion, causing lung and prostate cancers alongside renal tubular damage, the European PVC industry voluntarily eliminated cadmium stabilizers by March 2001, transitioning to non-toxic calcium-zinc or organotin options without performance deficits in most applications.[62][63][64] Regulatory scrutiny extended to pigments in plastics, with the EU's REACH framework restricting cadmium concentrations above 0.01% in consumer articles since 2019, though exemptions apply for durable goods like ceramics where migration risks remain negligible due to the pigments' insolubility and low bioavailability. In the United States, voluntary industry guidelines and state bans on cadmium in children's products have curtailed legacy uses, yet pigments endure in niche industrial contexts owing to irreplaceable properties; empirical leaching tests confirm minimal release under physiological conditions, contrasting with soluble cadmium salts.[65][66][67]Alloys, solders, and nuclear applications
Cadmium forms alloys with copper, zinc, lead, and silver that leverage its properties of high ductility, corrosion resistance, low melting temperature, and fatigue endurance for demanding industrial roles. Copper-cadmium alloys, typically containing 0.8–1.2% cadmium by weight, achieve approximately double the tensile strength and wear resistance of unalloyed copper while preserving over 90% of its electrical and thermal conductivity; these are employed in overhead electrical conductors, railway electrification wiring, and commutator components where elevated temperatures and mechanical stress prevail.[68][5] Zinc-cadmium alloys enhance bearing performance through a low coefficient of friction and superior fatigue resistance, suiting applications in aircraft engines and heavy machinery.[69][4] In solders and brazing fillers, cadmium lowers melting points and boosts capillary flow while imparting shear strength, particularly in silver-cadmium-zinc compositions used for joining metals in aerospace, defense, and electrical assemblies. Cadmium-zinc solders exhibit robust mechanical integrity under load, though their application has diminished since the 1990s due to regulatory restrictions on cadmium's toxicity, prompting shifts to cadmium-free alternatives like tin-silver-copper formulations.[70][71] Cadmium serves as a neutron absorber in nuclear reactors owing to its exceptionally high thermal neutron capture cross-section of about 2,450 barns for the isotope ^{113}Cd, enabling precise control of fission rates. It is deployed in control rods, burnable poisons, and shielding to suppress excess reactivity, reduce neutron flux gradients during operations like silicon doping, and mitigate radiation doses; however, cadmium's accumulation as a fission product poison and corrosion concerns in reactor environments have led to preferences for alternatives such as boron or hafnium in modern designs.[72][73][74]Semiconductors, photovoltaics, and emerging uses
Cadmium chalcogenides, such as cadmium telluride (CdTe), cadmium sulfide (CdS), and cadmium selenide (CdSe), serve as direct-bandgap semiconductors valued for their tunable optical properties and high electron mobility, enabling applications in photodetectors, light-emitting devices, and radiation sensors.[75] CdTe, in particular, is employed in X-ray and gamma-ray detectors due to its high atomic number and density, which enhance detection efficiency, while cadmium zinc telluride (CdZnTe) substrates are used in room-temperature radiation detectors for medical imaging and security applications.[76] CdS finds use in photoelectrochemical cells and heterojunction devices, leveraging its wide bandgap for window layers in photovoltaic structures. In photovoltaics, CdTe thin-film solar cells represent a significant commercial application, comprising approximately 3% of global photovoltaic production and 34% of the U.S. utility-scale market in 2022, with preliminary 2023 data indicating sustained growth.[77] These cells achieve laboratory efficiencies up to 22.3% as of 2023, incorporating cadmium selenide telluride (CdSeTe) alloys to improve near-infrared absorption and reduce back-contact recombination, though they remain below the theoretical limit of 31%.[78][79] First Solar, the primary gigawatt-scale producer, reported a domestic manufacturing capacity of 9.4 GWdc per year as of September 2024, benefiting from lower material costs and simpler deposition processes compared to crystalline silicon, despite challenges from cadmium's toxicity requiring stringent recycling protocols.[80][34] Emerging uses include CdSe quantum dots for optoelectronic devices, where their size-dependent emission enables efficient color conversion in displays and LEDs, as well as biomedical imaging via antibody conjugation for targeted fluorescence.[81][82] These dots are integrated into quantum-dot light-emitting diodes (QD-LEDs) for high color purity and brightness, though regulatory restrictions on cadmium content in consumer products have spurred development of alternatives, with cadmium-based variants persisting in high-performance niches like solar concentrators and photodetection.[83] Recent advances, such as Z-type ligands to mitigate surface defects, have enhanced stability in LED applications, underscoring cadmium's role in bridging performance gaps until non-toxic substitutes mature.[84]Biological Interactions and Health Effects
Lack of essential biological function
Cadmium is classified as a non-essential heavy metal with no established biological function in humans or other higher organisms. Unlike essential trace elements such as zinc or copper, which serve as cofactors in metalloenzymes critical for metabolism, respiration, and DNA synthesis, cadmium does not participate in any verified enzymatic or physiological processes necessary for life.[85][86] Extensive biochemical studies have failed to identify deficiency symptoms in cadmium-deprived mammals, further confirming its dispensability.[87] In humans, cadmium's accumulation primarily occurs through environmental exposure rather than any nutritional requirement, leading to its binding with proteins like metallothionein without contributing to homeostasis or cellular function.[88] Regulatory bodies, including the U.S. Environmental Protection Agency, explicitly describe cadmium as lacking biological utility in vertebrates, where it instead disrupts essential metal transport and induces oxidative stress.[86] Claims of potential essentiality, such as minor roles in rat metabolism or vascular health, remain unsubstantiated by controlled experiments and are contradicted by overwhelming evidence of toxicity even at trace levels.[89] A limited exception appears in certain marine microorganisms. In some diatom species, cadmium can substitute for zinc in the enzyme carbonic anhydrase (CDCA) under zinc-limited oceanic conditions, facilitating carbon dioxide hydration for photosynthesis and potentially influencing global carbon cycling.[90] This microbial adaptation, observed in experiments with species like Thalassiosira weissflogii, does not extend to multicellular life forms and underscores cadmium's opportunistic rather than essential role, as zinc remains the primary cofactor.[91] No analogous function has been demonstrated in terrestrial or mammalian systems, reinforcing cadmium's status as biologically superfluous and hazardous.[87]Toxicological mechanisms
Cadmium toxicity arises primarily from its high affinity for sulfhydryl (-SH) groups on proteins, enzymes, and DNA, leading to inactivation of critical biomolecules and disruption of cellular processes.[92] Unlike essential metals, cadmium lacks specific transporters but enters cells via divalent cation channels for calcium, zinc, or iron, such as DMT1 or ZIP transporters, mimicking these ions and displacing them from binding sites.[93] This substitution impairs enzyme function, for instance, by replacing zinc in metalloproteins like superoxide dismutase, exacerbating oxidative damage.[94] A central mechanism is the induction of oxidative stress, where cadmium generates reactive oxygen species (ROS) through Fenton-like reactions and mitochondrial dysfunction, overwhelming antioxidant systems like glutathione and catalase.[95] Depletion of glutathione occurs via cadmium's binding to its thiol groups, preventing ROS neutralization and promoting lipid peroxidation, protein carbonylation, and DNA strand breaks.[96] In renal proximal tubule cells, the primary target organ, cadmium binds to metallothionein for detoxification and storage, but chronic overload releases free cadmium ions, triggering endoplasmic reticulum stress, caspase activation, and apoptosis via both intrinsic (mitochondrial) and extrinsic pathways.[97] Genotoxicity contributes to cadmium's carcinogenic potential, classified as a Group 1 human carcinogen by the IARC, through indirect DNA damage from ROS and direct inhibition of repair enzymes like OGG1 and PARP by cadmium-protein adducts.[98] Epigenetic alterations, including hypomethylation of proto-oncogenes and hypermethylation of tumor suppressors, further amplify oncogenic signaling.[92] In the liver and testes, cadmium disrupts signal transduction (e.g., MAPK and NF-κB pathways) and hormone regulation, leading to inflammation and steroidogenesis impairment, respectively.[99] These multifaceted interactions underscore cadmium's non-threshold toxicity, with effects scaling by dose, duration, and co-exposures.[100]Human exposure routes and epidemiological evidence
Humans are exposed to cadmium primarily through two main routes: ingestion via contaminated food and water, and inhalation, with the latter being particularly significant for smokers due to cadmium accumulation in tobacco leaves. Food sources include shellfish, organ meats, leafy vegetables, and grains grown in cadmium-contaminated soils, often from phosphate fertilizers or industrial pollution; for non-smokers, dietary intake accounts for over 90% of total exposure in the general population. Occupational exposure occurs mainly through inhalation of cadmium dust or fumes in industries such as mining, smelting, battery manufacturing, and welding, where airborne concentrations can exceed 5 μg/m³, leading to acute or chronic uptake. Dermal absorption is minimal due to cadmium's poor skin penetration.[101][92][102] Epidemiological studies link chronic low-level cadmium exposure to renal tubular dysfunction, characterized by increased urinary β2-microglobulin and low-molecular-weight proteinuria, observed in populations near industrial sites or with high dietary intake, such as in Belgian areas with zinc mining history where urinary cadmium levels above 2 μg/g creatinine correlate with kidney damage. In Japan, the Itai-itai disease outbreak in the 1950s–1960s, affecting over 200 residents along the Jinzu River due to cadmium-contaminated irrigation water and rice, demonstrated severe osteomalacia, renal failure, and bone fractures, with causal evidence from elevated blood and urine cadmium (up to 100 μg/L) and histopathological findings. Cohort studies of smelters and battery workers show dose-dependent increases in lung cancer risk, with standardized mortality ratios up to 1.5–2.0 for exposures exceeding 1 mg/m³-years, supporting cadmium's classification as a Group 1 carcinogen by the International Agency for Research on Cancer based on both human and animal data.[103][104][105] Further evidence from population-based surveys, including the U.S. National Health and Nutrition Examination Survey (NHANES), associates urinary cadmium levels ≥0.5 μg/g creatinine with elevated risks of osteoporosis and fractures in postmenopausal women, with odds ratios of 1.2–1.7, attributed to cadmium-induced disruption of vitamin D metabolism and bone resorption. Cardiovascular effects are indicated by meta-analyses showing positive associations with hypertension (relative risk 1.2 per doubling of urinary cadmium) and incident heart failure or stroke, as seen in Swedish cohorts with environmental exposure where blood cadmium >0.5 μg/L predicted 20–30% higher event rates after adjusting for confounders like smoking and age. While these associations are consistent across studies, confounding by co-exposures such as lead or arsenic complicates strict causality attribution in non-occupational settings, though mechanistic evidence from animal models reinforces cadmium's role in endothelial damage and oxidative stress.[106][107][108]Environmental Distribution and Consequences
Emission sources and biogeochemical cycling
Cadmium enters the environment primarily through natural and anthropogenic pathways, with the latter dominating global emissions by at least an order of magnitude.[109] Natural sources include weathering of cadmium-bearing rocks, volcanic eruptions, forest fires, sea spray, and windblown soil dust, contributing an estimated 14.7 metric tons annually to atmospheric emissions in the European Union, though global natural fluxes are higher due to widespread geological occurrences.[110] Anthropogenic emissions stem mainly from non-ferrous metal production—particularly zinc, lead, copper, and cadmium smelting and refining—which accounts for the largest share, followed by fossil fuel combustion, waste incineration, and ferrous metal processing.[111] [112] Industrial activities contribute approximately 62% of total cadmium emissions worldwide.[113] Phosphate fertilizers represent a significant diffuse source, as cadmium impurities in phosphate rock (typically 10–100 mg/kg) are released during agricultural application, leading to gradual soil accumulation.[114] In recent decades, regulatory controls have reduced emissions; for instance, European cadmium air emissions declined by 33% from 2005 to 2019, with total releases dropping to levels comparable to natural background in some regions (around 20 metric tons per year).[115] Globally, however, mining and smelting remain primary hotspots, with emissions tied to zinc production volumes exceeding 6 million metric tons annually.[116] Cadmium's biogeochemical cycle has been profoundly altered by anthropogenic inputs since the Industrial Revolution, shifting from predominantly geological fluxes to human-dominated pathways.[117] In the atmosphere, cadmium particles—often bound to aerosols from combustion or smelting—undergo long-range transport before wet and dry deposition to soils and water bodies, where solubility depends on pH, redox conditions, and organic matter.[114] In soils, cadmium exhibits low mobility but persists due to strong adsorption to clays and iron oxides; however, acidification from pollution or fertilization enhances bioavailability, facilitating plant root uptake and entry into terrestrial food webs.[118] Aquatic cycling mirrors nutrient dynamics, particularly phosphate, with cadmium displaying a nutrient-like profile in oceans: surface depletion via phytoplankton incorporation, subsurface regeneration during organic matter remineralization, and deep-water scavenging by sulfides or particulates.[119] Cadmium sulfides play a key role in sedimentary sinks, precipitating under sulfidic conditions and limiting remobilization, though coastal wetlands experience flux variations tied to hydrology and microbial activity.[120] Biologically, non-essential uptake occurs via inadvertent incorporation into metal-binding proteins, amplifying trophic transfer in both marine and freshwater systems, with minimal volatilization or long-term burial mitigating atmospheric recycling.[121] Overall, anthropogenic perturbations have increased cadmium residence times in surface environments, elevating exposure risks without corresponding natural attenuation mechanisms.[122]Bioaccumulation in organisms
Cadmium bioaccumulates in organisms across trophic levels due to its chemical similarity to essential metals like zinc and calcium, enabling uptake via transport proteins, coupled with slow excretion rates and binding to intracellular ligands such as metallothioneins. This results in tissue concentrations that increase with exposure duration and exceed ambient environmental levels, particularly in organs involved in detoxification. In aquatic invertebrates, including mollusks and crustaceans, cadmium accumulates primarily in digestive glands, gills, and exoskeletons, with bioconcentration factors often ranging from 10^3 to 10^5 relative to water concentrations under chronic low-level exposure.[123][124] In fish, cadmium uptake occurs via gills from water and through diet, leading to highest concentrations in kidneys and liver—organs that sequester the metal via metallothionein induction for detoxification—followed by gills, spleen, and muscle. For instance, in species like common carp (Cyprinus carpio) and Nile tilapia (Oreochromis niloticus), kidney burdens can reach 10-100 times those in muscle after prolonged exposure, reflecting renal filtration and reabsorption dynamics.[125][123][126] Trophic transfer shows evidence of biomagnification in some freshwater systems, with enrichment factors up to 15 across two trophic links from algae to predatory fish, driven by efficient assimilation from invertebrate prey. However, in marine and certain pelagic food webs, cadmium often undergoes biodilution or stable transfer without net magnification, as higher predators regulate uptake via dietary avoidance or enhanced excretion.[127][128][129] Terrestrial plants absorb cadmium from soil via roots, primarily through symplastic pathways mimicking zinc transporters, with translocation to edible shoots varying by species; hyperaccumulators like Thlaspi caerulescens can achieve foliar levels >1000 mg/kg dry weight, while crops such as rice and wheat show root-to-shoot ratios of 0.1-0.5 under neutral pH conditions. In terrestrial animals, including mammals and birds, cadmium concentrates in kidneys (up to 50-100 mg/kg in chronically exposed livestock) and liver, where half-lives exceed 10-30 years due to minimal biliary excretion and renal tubular retention. Bioaccumulation factors in soil invertebrates like earthworms can reach 5-10 relative to soil cadmium, facilitating transfer to predators.[130][95] Overall, while cadmium's persistence drives accumulation, organism-specific detoxification mechanisms, such as metallothionein synthesis, modulate net retention without consistent biomagnification across diverse ecosystems.[131][132]Ecosystem and soil impacts
Cadmium accumulation in soils impairs soil quality by reducing fertility and altering physicochemical properties, such as increasing acidity and decreasing cation exchange capacity, primarily due to its high solubility and mobility in neutral to acidic environments.[133] This contamination disrupts microbial communities, with studies showing significant shifts in bacterial diversity and composition; for instance, cadmium exposure increases the relative abundance of Proteobacteria and Gemmatimonadetes while decreasing Nitrospirae, leading to reduced overall microbial biomass and impaired functions like nutrient cycling and organic matter decomposition.[134] Fungal communities are less affected than bacterial ones, but cadmium still hampers soil enzyme activities essential for biogeochemical processes.[135] In plants, cadmium induces phytotoxicity by inhibiting root growth, reducing chlorophyll content, and causing oxidative stress through reactive oxygen species generation, which damages cellular structures and disrupts photosynthesis and nutrient assimilation.[136] This results in stunted growth, chlorosis, and decreased biomass, with uptake varying by soil pH and organic matter; lower pH enhances bioavailability, exacerbating toxicity in crops like rice and wheat.[114] Cadmium also competes with essential elements like zinc and iron, further limiting plant productivity and entering the food web via root absorption.[136] Soil fauna, including earthworms and nematodes, experience cadmium-induced oxidative damage, growth inhibition, and reproductive declines, contributing to biodiversity loss and altered trophic interactions.[137] Bioaccumulation amplifies these effects up the food chain, as cadmium persists in organisms without biomagnification but with high retention in kidneys and livers of herbivores and predators, disrupting ecosystem stability and services like soil aeration and pollination.[138] In contaminated agroecosystems, these impacts reduce overall resilience, with EPA ecological soil screening levels set at 35 mg/kg for terrestrial plants and 58 mg/kg for soil invertebrates to mitigate risks.[139]Risk Management and Exposure Controls
Occupational safety measures
Occupational exposure to cadmium occurs primarily through inhalation of dusts, fumes, or mists in industries such as battery production, metal welding, electroplating, and pigment manufacturing, necessitating stringent controls to prevent respiratory, renal, and carcinogenic effects.[140] The U.S. Occupational Safety and Health Administration (OSHA) mandates under 29 CFR 1910.1027, adopted in 1992, a permissible exposure limit (PEL) of 5 micrograms per cubic meter (µg/m³) of air as an 8-hour time-weighted average, with an action level of 2.5 µg/m³ triggering additional requirements.[141] Employers must conduct initial and periodic exposure monitoring using personal breathing zone samples to assess compliance, with methods validated per OSHA protocols.[142] Engineering controls form the primary defense, prioritizing substitution with less hazardous materials where feasible, enclosure of processes, and local exhaust ventilation systems to capture cadmium at the source before dispersion.[143] Work practice controls include minimizing cadmium handling, using wet methods to suppress dust, and prohibiting practices like dry sweeping that resuspend particles.[144] If these measures fail to reduce exposure below the PEL, administrative controls such as job rotation and respiratory protection programs are required, with the latter following OSHA's 29 CFR 1910.134 standard for fit-testing and medical clearance.[141] Personal protective equipment (PPE) includes impermeable clothing, gloves, and footwear to prevent skin contact, with contaminated items laundered or disposed of on-site to avoid take-home exposure.[141] Respirators range from half-facepiece air-purifying types with high-efficiency particulate air (HEPA) filters for levels up to 10 times the PEL to supplied-air respirators for higher concentrations or unknown risks.[144] Hygiene facilities mandate separate change rooms, showers, and handwashing stations, with prohibitions on eating, drinking, or smoking in exposure areas to curb incidental ingestion.[142] Training programs must inform workers of cadmium hazards, safe handling, emergency procedures, and recognition of overexposure symptoms like metallic taste or dyspnea, delivered initially and annually.[145] Medical surveillance is compulsory for employees exposed at or above the action level for 30 or more days per year, encompassing initial examinations, annual biological monitoring (e.g., urinary cadmium and beta-2-microglobulin levels), chest X-rays every five years for long-term exposed workers, and pulmonary function tests to detect early kidney or lung impairment.[141] Records of monitoring and health data must be retained for 30 years, with multiple physician review options for abnormal results to ensure objective assessment.[146] The National Institute for Occupational Safety and Health (NIOSH) endorses controlling exposures to the lowest feasible level, viewing cadmium as a probable carcinogen since 1984, though OSHA's PEL remains the enforceable benchmark.[147]Consumer product restrictions
In the European Union, the Restriction of Hazardous Substances (RoHS) Directive (2002/95/EC, as amended) prohibits cadmium concentrations exceeding 0.01% by weight (100 ppm) in homogeneous materials of electrical and electronic equipment placed on the market after July 1, 2006, with exemptions for specific applications such as certain LED chips limited to 1 mg per phosphor weight or 10 micrograms per square millimeter of light-emitting area, periodically reviewed and narrowed based on technological assessments.[148][149][150] Under the REACH Regulation (EC) No 1907/2006, Annex XVII entry 23 restricts cadmium to less than 0.01% by weight in plastics, paints, varnishes, and jewelry articles, with a full ban on its intentional use in these consumer products effective December 20, 2011, except for antiques or recovered materials in specific cases; violations remain common in imported jewelry and seasonal goods, prompting enhanced enforcement.[151][152][153] In the United States, the Consumer Product Safety Improvement Act (CPSIA) of 2008, enforced by the Consumer Product Safety Commission (CPSC), limits soluble cadmium to 75 ppm in surface coatings of children's toys and child care articles manufactured after August 14, 2009, and sets extraction limits of no more than 200 µg total cadmium from substrates in a 24-hour test per ASTM F963 standards; additional restrictions apply to children's jewelry, with ongoing seizures of non-compliant imports exceeding these thresholds.[154][155][156] Globally, similar limits appear in frameworks like Canada's Children's Jewellery Regulations (under the Canada Consumer Product Safety Act), capping total cadmium at 130 mg/kg in jewelry, while international trade often aligns with EU or US standards to facilitate compliance; however, enforcement varies, with higher violation rates in non-OECD countries for cadmium in pigments and stabilizers.[157]Monitoring and mitigation technologies
Monitoring of cadmium concentrations in environmental media, occupational settings, and biological samples primarily relies on atomic absorption spectroscopy (AAS) and inductively coupled plasma mass spectrometry (ICP-MS), which offer high sensitivity for trace-level detection in air, water, soil, and tissues.[158][159] ICP-MS provides multi-element analysis with detection limits below 0.1 µg/L for cadmium in water and blood, making it suitable for routine screening, while graphite furnace AAS (GFAAS) excels in direct analysis of complex matrices like seawater after minimal preconcentration.[160][161] In occupational environments, the U.S. Occupational Safety and Health Administration (OSHA) mandates initial and periodic air monitoring to ensure exposures remain below the permissible exposure limit of 5 µg/m³ as an 8-hour time-weighted average, with action levels at 2.5 µg/m³ triggering medical surveillance.[141] Biological monitoring involves measuring cadmium in blood (indicative of recent exposure) or urine (reflecting body burden), with thresholds such as urinary cadmium exceeding 3 µg/g creatinine signaling potential kidney effects in workers.[162] Emerging field-portable technologies, such as X-ray fluorescence (XRF) analyzers, enable real-time airborne cadmium detection alongside other heavy metals, supporting rapid compliance assessments in industrial sites.[163] Mitigation technologies for cadmium emphasize source control, extraction, and stabilization to reduce bioavailability and environmental release. Phytoremediation uses hyperaccumulator plants like Thlaspi caerulescens or maize enhanced with chelators (e.g., EDTA) to extract cadmium from contaminated soils, achieving removal rates up to 20-50% over multiple growth cycles by promoting root uptake and translocation to harvestable biomass.[164][165] For groundwater, permeable reactive barriers incorporating adsorbents like zero-valent iron or biochar intercept cadmium plumes, with reported retention efficiencies exceeding 90% under controlled flow conditions.[166] Soil washing with acids or chelating agents solubilizes cadmium for separation, demonstrating 70-95% removal from moderately contaminated sites, though it requires post-treatment to manage leachates.[167] In agricultural contexts, lime or phosphate amendments stabilize cadmium in soils by forming insoluble precipitates, reducing plant uptake by 30-60% and mitigating dietary exposure risks without excavating topsoil.[168] Industrial air emissions are mitigated via electrostatic precipitators and wet scrubbers, which capture cadmium-bearing particulates with efficiencies over 99% in non-ferrous metal smelters.[144] These approaches prioritize cost-effective, site-specific interventions, with phytoremediation favored for large-scale, low-concentration pollution due to its lower energy demands compared to physicochemical methods.[169]Regulatory Frameworks and Debates
Global and international standards
The World Health Organization (WHO) classifies cadmium as a Group 1 human carcinogen, exerting toxic effects on the kidneys, skeletal system, and respiratory tract, and provides guideline values for environmental media to limit population exposure. For drinking water, WHO recommends a maximum of 3 μg/L, derived from renal toxicity thresholds and assuming a 60 kg adult consuming 2 L daily. Ambient air quality guidelines from WHO account for cadmium's deposition and bioaccumulation in agricultural soils, emphasizing long-term inhalation risks below 0.005 μg/m³ as an annual mean to prevent chronic health impacts. These values prioritize empirical data on dose-response relationships from epidemiological studies, though they represent provisional tolerable intakes rather than enforceable limits.[170][114][171] The Codex Alimentarius Commission, administered jointly by the Food and Agriculture Organization (FAO) and WHO, establishes maximum levels (MLs) for cadmium in foods under the General Standard for Contaminants and Toxins in Food and Feed (CXS 193-1995) to reduce dietary intake, which accounts for over 90% of non-occupational exposure in many populations. Specific MLs include 0.4 mg/kg for rice, 0.1 mg/kg for other cereals, 0.05 mg/kg for stem and root vegetables, 0.2 mg/kg for leafy vegetables, and 0.3–0.7 mg/kg for chocolate depending on cocoa content (up to 30% or 30–50% solids). These levels, set between 2001 and 2006 based on joint FAO/WHO expert committee evaluations of global intake data, aim to keep provisional tolerable weekly intake below 2.5 μg/kg body weight, though revisions continue for commodities like quinoa and spices as of 2024.[172][173] For occupational exposure, the International Labour Organization (ILO) endorses protective measures under Convention No. 155 on Occupational Safety and Health (1981) and related chemicals conventions, recommending engineering controls, monitoring, and personal protective equipment to minimize cadmium dust and fume inhalation in industries like smelting and battery production. Internationally referenced limits include a time-weighted average of 0.01 mg/m³ for cadmium and compounds, aligned with carcinogenicity classifications and biological monitoring via urine cadmium levels below 5 μg/g creatinine. The ILO's International Chemical Safety Cards further specify this threshold, noting acute risks from high exposures exceeding 0.5 mg/m³. Unlike binding treaties for persistent organic pollutants, no comprehensive global convention mandates cadmium emission reductions; instead, UNEP's chemicals management initiatives under the Strategic Approach to International Chemicals Management (SAICM) promote data sharing and risk assessments for heavy metals like cadmium.[174][175][176]National and regional regulations
In the United States, the Occupational Safety and Health Administration (OSHA) establishes a permissible exposure limit (PEL) for cadmium of 5 micrograms per cubic meter (µg/m³) as an 8-hour time-weighted average, with an action level of 2.5 µg/m³ triggering medical surveillance and exposure monitoring requirements across general industry, construction, and maritime sectors.[177][142] The Environmental Protection Agency (EPA) sets a maximum contaminant level (MCL) of 0.005 milligrams per liter (mg/L) for cadmium in drinking water under the Safe Drinking Water Act, alongside national emission standards for hazardous air pollutants targeting cadmium from industrial sources.[178] The Food and Drug Administration (FDA) monitors cadmium in foods and food contact materials but imposes no specific authorization for its use as a color additive or direct additive, relying on general safety assessments to limit residues.[179] In the European Union, the Restriction of Hazardous Substances (RoHS) Directive (2011/65/EU) prohibits cadmium concentrations exceeding 0.01% by weight in electrical and electronic equipment, with limited exemptions extended in 2024 for its use in recovered rigid polyvinyl chloride (PVC) for doors and windows to facilitate recycling.[148][180] Under the REACH Regulation, cadmium is registered and restricted in various applications, including pigments, stabilizers, and coatings, due to its classification as a carcinogen and reproductive toxicant, mandating authorization for high-volume uses.[181] The EU also enforces maximum levels for cadmium in foodstuffs, such as 0.2 mg/kg in chocolate and 0.05 mg/kg in leafy vegetables, as established by Commission Regulation (EU) 2021/1317, reflecting efforts to curb dietary exposure amid evidence of exceedances in certain populations.[182] China's national standards under GB 2762-2022 specify maximum contaminant levels for cadmium in foods, including 0.2 mg/kg in rice and 0.1 mg/kg in most vegetables, with additional limits in the China RoHS framework (effective 2024) requiring declaration of cadmium content exceeding 0.01% in electrical and electronic products.[183][184] For fertilizers, national standards permit up to 60 mg/kg cadmium in phosphate products, though studies indicate these thresholds may insufficiently protect soil and food chains given elevated uptake risks.[185] Emerging standards, such as those for inks under public comment in 2024, cap cadmium at 100 mg/kg to address migration into packaging.[186] Japan maintains stringent controls informed by historical cadmium pollution incidents, with Food Sanitation Law standards limiting cadmium to 0.4 mg/kg in rice and lower thresholds in other foods like polished rice at 0.1 mg/kg, alongside extraction limits of 0.1 µg/ml in food contact materials such as ceramics.[187][188] Occupational exposure limits align closely with international benchmarks, emphasizing monitoring in battery and pigment production, where cadmium use has been phased down.[189]| Region/Country | Occupational PEL (8-hour TWA, µg/m³) | Drinking Water MCL (mg/L) | Key Product Restrictions |
|---|---|---|---|
| United States | 5 (OSHA)[177] | 0.005 (EPA)[178] | Prohibited as food additive (FDA)[179] |
| European Union | Varies; 1-5 under Carcinogens Directive[190] | 0.005 (aligned with WHO) | <0.01% in electronics (RoHS)[148] |
| China | Not uniformly specified; site-specific | Varies by standard | Declaration >0.01% in electronics (China RoHS)[184] |
| Japan | ~5 (aligned with JSOH)[189] | 0.003 | Strict in rice/food contact (0.1-0.4 mg/kg)[187] |