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Cerium
Cerium SC Gad, Gad Consulting Services, Cary, NC, USA Ó 2014 Elsevier Inc. All rights reserved. This article is a revision of the previous edition article by Shayne C. Gad, volume 1, pp 502–503, Ó 2005, Elsevier Inc.
l
Name: Cerium Chemical Abstracts Service Registry Number: 7440-45-1 l Synonyms: Cerium, EINECS 231-154-9, UNII-30K4522N6T l Molecular Formula: Ce3þ, Ce4þ l
Exposure and Exposure Monitoring
Background Information Cerium is a rare earth metal and the most abundant member of the lanthanide series discovered by Jons J. Berzelius and W. von Hisinger in 1803 in Sweden. Berzelius and Hisinger discovered the new element in a rare reddish-brown mineral now known as cerite, a cerium–lanthanide silicate. Although they could not isolate the pure metal, they found that cerium had two oxidation states: trivalent state (Ce3þ, cerous, usually orangered) and the tetravalent state (Ce4þ, ceric, usually colorless). Cerium is the only material known to have a solid-state critical point.
Uses Cerium is used in metallurgy as a stabilizer in alloys and in welding electrodes; in glass as a polishing agent, decolorizer, and to render glass opaque to near-ultraviolet radiation. It is also used in ceramics and as a catalyst. Cerium is used as a component of some diesel fuel additives, and may be added to residual fuel oils to improve combustion. Cerium is found in portable rechargeable batteries.
Environmental Fate and Behavior Although cerium is a rare earth element, it is relatively abundant in the earth’s crust. It makes up about 0.0046% of the Earth’s crust by weight and ranks 25th in occurrence at an average distribution of 20–60 ppm. Cerium is a malleable, soft, ductile, iron-gray metal, slightly harder than lead. It is very reactive and readily tarnishes in the air. Cerium oxidizes slowly in cold water and rapidly in hot water. It dissolves in acids. Cerium can burn when heated or scratched with a knife. Cerium is not expected to exist in elemental form in the environment since it is a reactive metal. Cerium is dumped in the environment in many different places, mainly by petrolproducing industries. It can also enter the environment when household equipment is thrown away. Cerium compounds exist solely in particulate form if release into air and not expected to volatilize. Water-soluble cerium compounds usually have a pKa of 8.5, which indicates that the hydrated Ce3þ ion will remain in solution at environmental pHs of 4–9. The ion is expected to hydrolyze and polymerize at
Encyclopedia of Toxicology, Volume 1
environmental pH and may precipitate out of solution. Thus, cerium will gradually accumulate in soils and water, which eventually leads to increasing concentrations in humans, animals, and soil particles.
Inhalation, dermal, and oral are the possible exposure routes. Exposure to commercially used cerium compounds is most likely through exposure to cerium oxide.
Toxicokinetics Cerium is poorly absorbed by the intestine following oral exposure in animals, except for water-soluble cerium compounds and cerium oxide. As poorly soluble particles, cerium oxide may dissolve slowly from the lung into systemic circulation and is observed in the liver, skeleton, and tracheobronchial lymph nodes. Cerium has also been observed to be localized in the cell, particularly in the lysosomes, where it is concentrated and precipitated in an insoluble form in association with phosphorus. As an element, cerium is neither created nor destroyed within the body. The particular cerium compounds, such as cerium chloride and cerium oxide, may be altered as a result of various chemical reactions within the body, particularly dissolution. Following inhalation exposure, the initial rapid elimination of insoluble cerium from the body is due primarily to transport up to the respiratory tract via the mucociliary escalator and eventual swallowing of the material. Initial short-term clearance rates range from 35 to 95% of initial cerium body burden, depending on the species tested and length of clearance time investigated. Elimination of orally administered soluble cerium has been shown to be age dependent in animals. The cerium may remain in the intestinal cells, may not be available systemically, and may eventually be eliminated in the feces. Cerium is capable of crossing the placenta and entering the fetal circulation in mice, but the amounts found in the uterus and placenta were generally less than 5% of the maternal body burden and decreased rapidly with increased time after exposure.
Mechanism of Toxicity Cerium resembles aluminum in its biologic and chemical properties. Cerium and cerium compounds have low to moderate toxicity unless the associated anions are toxic. Intratracheally administered nanoparticles tend to accumulate in liver and cause damage there.
http://dx.doi.org/10.1016/B978-0-12-386454-3.00826-5
773
774
Cerium
Acute and Short-Term Toxicity (or Exposure) Animal The LD50 values reported in rats ranged from 4 to 50 mg kg1 for cerium nitrate with female rats being more sensitive than males. After peritoneal injection, the LD50 of cerium nitrate was 470 mg kg1 in female mice and 290 mg kg1 in female rats; the LD50 of cerium chloride was 353 mg kg1 in mice and 103 mg kg1 in guinea pigs. The oral toxicity of cerium nitrate was much lower (LD50 of 4200 mg kg1 in female rats and 1178 mg kg1 in female mice) than after intravenous or intraperitoneal administration. The LD50 of ingested cerium oxide could not be determined in rats when delivered at a dose of 1000 or 5000 mg kg1. An LD50 of 622 mg kg1 has been reported for cerium oxide ingested by mice. The LC50 after inhalation of cerium oxide in rats was greater than 50 mg m3. The primary targets after inhalation of cerium are the lung and the associated lymph nodes; other organs could be affected via clearance through the blood. Studies of cerium injected systemically have shown that, once in the circulation, cerium can cause liver toxicity with a no observed adverseeffect level of 1 mg kg1 after a single intravenous injection and a lowest observed adverse effect level (LOAEL) of 2 mg kg1 for effects on liver detoxifying enzymes. Effects on other organs where cerium can accumulate (such as spleen, bones, and kidney) have not been studied. A single-dose study on the effects of in utero intravenous administration reported reduced weight in newborn mouse pups, with an LOAEL of 80 mg kg1. Cerium has been found to depress certain behaviors in mice administered this chemical, and cerium administered to pregnant mice on day 7 or 12 of gestation or 2 days postpartum caused significant decreases in open-field activity of offspring. Fetal growth was impaired, as evidenced by weight decreases of 7–19%. The potential carcinogenicity of cerium-containing particles has not been studied in conventional rodent bioassays; in vivo mutagenicity studies have been negative.
Human Cerium can increase blood coagulation rate and produce gastrointestinal effects. Inhalation can lead to polycythemia.
associated with accumulation of cerium in particles, the role of cerium in this complex disease is unclear relative to other metals or gases to which workers may also have been exposed.
Immunotoxicity No relevant human or animal data are available regarding immunotoxicity in cerium or cerium compounds.
Reproductive Toxicity A cross-fostering design was employed to separate effects of prenatal and postnatal exposure following a single subcutaneous dose of cerium citrate (80 mg kg1) in pregnant female mice. Analysis revealed that neonatal weight was reduced both in offspring exposed to cerium in utero and in the offspring of mothers receiving cerium during lactation. Cerium also appeared to affect maternal-offspring interaction: Pups exposed prenatally to cerium were retrieved in less time than control pups.
Genotoxicity In vitro mutagenicity studies have been negative. Other cerium compounds, such as cerium chloride observed no induction DNA damage in two strains of Bacillus subtilis by using rec-assay, but cerium nitrate was reported to induce chromosomal breaks and reduce the mitotic index in rat bone marrow in vivo, and cerium sulfate was reported to cause differential destaining of chromosomal segments in plants. No information was located regarding genotoxic effects of cerium and cerium compounds in humans.
Carcinogenicity Data regarding the carcinogenicity of cerium compounds in humans or experimental animals are unavailable. In accordance with US Environmental Protection Agency, cerium and cerium compounds are classified as “inadequate information to assess the carcinogenic potential” in humans.
Chronic Toxicity (or Exposure) Animal
Clinical Management
An animal inhalation study involved exposure of rats to cerium oxide particles substantially larger than those in diesel emission. The exposure concentrations ranged between 5 and 500 mg m3 for 13 weeks. Effects observed included lung discoloration, enlargement of lymph nodes, and increased lung and spleen weight at all concentrations.
Treatments are addressed symptomatically.
Human
Exposure Standards and Guidelines
Case reports of workers occupationally exposed to rare earth metals (including cerium) describe a condition termed rare earth pneumoconiosis with pathologic features including interstitial fibrosis, granulomatosis, and bilateral nodular chest x-ray infiltrates. Although the disease sometimes is
No standards have been recommended for elemental cerium, cerium compounds, or any other lanthanides because either suitable data for setting a standard, such as inhalation studies or studies on these compounds are lacking. However, because of the accumulating evidence of induction of fibrosis with the
Ecotoxicity Toxicity to aquatic species is dependent upon the particle size.
Cerium
lanthanides and their expanding use, the exposure should probably be limited to 1 mg m3.
See also: Aluminum; Metals.
Further Reading Arvela, P., Kraul, H., Stenback, F., Pelkonen, O., 1991. The cerium-induced liver injury and oxidative drug metabolism in DBA/2 and C57BL/6 mice. Toxicology 69, 1–9. Berry, J.P., Meignan, M., Escaig, F., Galle, P., 1988. Inhaled soluble aerosols insolubilised by lysosomes of alveolar cells. Application to some toxic compounds; electron microprobe and ion microprobe studies. Toxicology 14, 127–139.
775
Binghma, E., Cohrssen, B., Powell, C.H., 2001. Patty’s Toxicology, fifth ed. A WileyInterscience Publication, New York. Biswas, A., Gaiser, B.K., Jepson, M.A., Lead, J.R., Rosenkranz, P., Stone, V., 2011. Effects of silver and Cerium dioxide micro- and nano-sized particles on Daphni. J. Environ. Monit. 5, 1227–1235. Nalabotu, S.K., Kolli, M.B., Triest, W.E., Ma, J.Y., Manne, N.D.P.K., 2011. Intratracheal instillation of cerium oxide nanoparticles induces hepatic toxicity. Nanomedicine 6, 2327–2335.
Relevant Websites http://www.healtheffects.org – Evaluation of Human Health Risk from Cerium Added to Diesel Fuel. Health Effects Institute Communication 9 (August 2001). http://www.chemicool.com/elements/cerium.html – "Cerium." Chemicool Periodic Table. Chemicool.com. (June 2011)
l
Name: Cerium Chemical Abstracts Service Registry Number: 7440-45-1 l Synonyms: Cerium, EINECS 231-154-9, UNII-30K4522N6T l Molecular Formula: Ce3þ, Ce4þ l
Exposure and Exposure Monitoring
Background Information Cerium is a rare earth metal and the most abundant member of the lanthanide series discovered by Jons J. Berzelius and W. von Hisinger in 1803 in Sweden. Berzelius and Hisinger discovered the new element in a rare reddish-brown mineral now known as cerite, a cerium–lanthanide silicate. Although they could not isolate the pure metal, they found that cerium had two oxidation states: trivalent state (Ce3þ, cerous, usually orangered) and the tetravalent state (Ce4þ, ceric, usually colorless). Cerium is the only material known to have a solid-state critical point.
Uses Cerium is used in metallurgy as a stabilizer in alloys and in welding electrodes; in glass as a polishing agent, decolorizer, and to render glass opaque to near-ultraviolet radiation. It is also used in ceramics and as a catalyst. Cerium is used as a component of some diesel fuel additives, and may be added to residual fuel oils to improve combustion. Cerium is found in portable rechargeable batteries.
Environmental Fate and Behavior Although cerium is a rare earth element, it is relatively abundant in the earth’s crust. It makes up about 0.0046% of the Earth’s crust by weight and ranks 25th in occurrence at an average distribution of 20–60 ppm. Cerium is a malleable, soft, ductile, iron-gray metal, slightly harder than lead. It is very reactive and readily tarnishes in the air. Cerium oxidizes slowly in cold water and rapidly in hot water. It dissolves in acids. Cerium can burn when heated or scratched with a knife. Cerium is not expected to exist in elemental form in the environment since it is a reactive metal. Cerium is dumped in the environment in many different places, mainly by petrolproducing industries. It can also enter the environment when household equipment is thrown away. Cerium compounds exist solely in particulate form if release into air and not expected to volatilize. Water-soluble cerium compounds usually have a pKa of 8.5, which indicates that the hydrated Ce3þ ion will remain in solution at environmental pHs of 4–9. The ion is expected to hydrolyze and polymerize at
Encyclopedia of Toxicology, Volume 1
environmental pH and may precipitate out of solution. Thus, cerium will gradually accumulate in soils and water, which eventually leads to increasing concentrations in humans, animals, and soil particles.
Inhalation, dermal, and oral are the possible exposure routes. Exposure to commercially used cerium compounds is most likely through exposure to cerium oxide.
Toxicokinetics Cerium is poorly absorbed by the intestine following oral exposure in animals, except for water-soluble cerium compounds and cerium oxide. As poorly soluble particles, cerium oxide may dissolve slowly from the lung into systemic circulation and is observed in the liver, skeleton, and tracheobronchial lymph nodes. Cerium has also been observed to be localized in the cell, particularly in the lysosomes, where it is concentrated and precipitated in an insoluble form in association with phosphorus. As an element, cerium is neither created nor destroyed within the body. The particular cerium compounds, such as cerium chloride and cerium oxide, may be altered as a result of various chemical reactions within the body, particularly dissolution. Following inhalation exposure, the initial rapid elimination of insoluble cerium from the body is due primarily to transport up to the respiratory tract via the mucociliary escalator and eventual swallowing of the material. Initial short-term clearance rates range from 35 to 95% of initial cerium body burden, depending on the species tested and length of clearance time investigated. Elimination of orally administered soluble cerium has been shown to be age dependent in animals. The cerium may remain in the intestinal cells, may not be available systemically, and may eventually be eliminated in the feces. Cerium is capable of crossing the placenta and entering the fetal circulation in mice, but the amounts found in the uterus and placenta were generally less than 5% of the maternal body burden and decreased rapidly with increased time after exposure.
Mechanism of Toxicity Cerium resembles aluminum in its biologic and chemical properties. Cerium and cerium compounds have low to moderate toxicity unless the associated anions are toxic. Intratracheally administered nanoparticles tend to accumulate in liver and cause damage there.
http://dx.doi.org/10.1016/B978-0-12-386454-3.00826-5
773
774
Cerium
Acute and Short-Term Toxicity (or Exposure) Animal The LD50 values reported in rats ranged from 4 to 50 mg kg1 for cerium nitrate with female rats being more sensitive than males. After peritoneal injection, the LD50 of cerium nitrate was 470 mg kg1 in female mice and 290 mg kg1 in female rats; the LD50 of cerium chloride was 353 mg kg1 in mice and 103 mg kg1 in guinea pigs. The oral toxicity of cerium nitrate was much lower (LD50 of 4200 mg kg1 in female rats and 1178 mg kg1 in female mice) than after intravenous or intraperitoneal administration. The LD50 of ingested cerium oxide could not be determined in rats when delivered at a dose of 1000 or 5000 mg kg1. An LD50 of 622 mg kg1 has been reported for cerium oxide ingested by mice. The LC50 after inhalation of cerium oxide in rats was greater than 50 mg m3. The primary targets after inhalation of cerium are the lung and the associated lymph nodes; other organs could be affected via clearance through the blood. Studies of cerium injected systemically have shown that, once in the circulation, cerium can cause liver toxicity with a no observed adverseeffect level of 1 mg kg1 after a single intravenous injection and a lowest observed adverse effect level (LOAEL) of 2 mg kg1 for effects on liver detoxifying enzymes. Effects on other organs where cerium can accumulate (such as spleen, bones, and kidney) have not been studied. A single-dose study on the effects of in utero intravenous administration reported reduced weight in newborn mouse pups, with an LOAEL of 80 mg kg1. Cerium has been found to depress certain behaviors in mice administered this chemical, and cerium administered to pregnant mice on day 7 or 12 of gestation or 2 days postpartum caused significant decreases in open-field activity of offspring. Fetal growth was impaired, as evidenced by weight decreases of 7–19%. The potential carcinogenicity of cerium-containing particles has not been studied in conventional rodent bioassays; in vivo mutagenicity studies have been negative.
Human Cerium can increase blood coagulation rate and produce gastrointestinal effects. Inhalation can lead to polycythemia.
associated with accumulation of cerium in particles, the role of cerium in this complex disease is unclear relative to other metals or gases to which workers may also have been exposed.
Immunotoxicity No relevant human or animal data are available regarding immunotoxicity in cerium or cerium compounds.
Reproductive Toxicity A cross-fostering design was employed to separate effects of prenatal and postnatal exposure following a single subcutaneous dose of cerium citrate (80 mg kg1) in pregnant female mice. Analysis revealed that neonatal weight was reduced both in offspring exposed to cerium in utero and in the offspring of mothers receiving cerium during lactation. Cerium also appeared to affect maternal-offspring interaction: Pups exposed prenatally to cerium were retrieved in less time than control pups.
Genotoxicity In vitro mutagenicity studies have been negative. Other cerium compounds, such as cerium chloride observed no induction DNA damage in two strains of Bacillus subtilis by using rec-assay, but cerium nitrate was reported to induce chromosomal breaks and reduce the mitotic index in rat bone marrow in vivo, and cerium sulfate was reported to cause differential destaining of chromosomal segments in plants. No information was located regarding genotoxic effects of cerium and cerium compounds in humans.
Carcinogenicity Data regarding the carcinogenicity of cerium compounds in humans or experimental animals are unavailable. In accordance with US Environmental Protection Agency, cerium and cerium compounds are classified as “inadequate information to assess the carcinogenic potential” in humans.
Chronic Toxicity (or Exposure) Animal
Clinical Management
An animal inhalation study involved exposure of rats to cerium oxide particles substantially larger than those in diesel emission. The exposure concentrations ranged between 5 and 500 mg m3 for 13 weeks. Effects observed included lung discoloration, enlargement of lymph nodes, and increased lung and spleen weight at all concentrations.
Treatments are addressed symptomatically.
Human
Exposure Standards and Guidelines
Case reports of workers occupationally exposed to rare earth metals (including cerium) describe a condition termed rare earth pneumoconiosis with pathologic features including interstitial fibrosis, granulomatosis, and bilateral nodular chest x-ray infiltrates. Although the disease sometimes is
No standards have been recommended for elemental cerium, cerium compounds, or any other lanthanides because either suitable data for setting a standard, such as inhalation studies or studies on these compounds are lacking. However, because of the accumulating evidence of induction of fibrosis with the
Ecotoxicity Toxicity to aquatic species is dependent upon the particle size.
Cerium
lanthanides and their expanding use, the exposure should probably be limited to 1 mg m3.
See also: Aluminum; Metals.
Further Reading Arvela, P., Kraul, H., Stenback, F., Pelkonen, O., 1991. The cerium-induced liver injury and oxidative drug metabolism in DBA/2 and C57BL/6 mice. Toxicology 69, 1–9. Berry, J.P., Meignan, M., Escaig, F., Galle, P., 1988. Inhaled soluble aerosols insolubilised by lysosomes of alveolar cells. Application to some toxic compounds; electron microprobe and ion microprobe studies. Toxicology 14, 127–139.
775
Binghma, E., Cohrssen, B., Powell, C.H., 2001. Patty’s Toxicology, fifth ed. A WileyInterscience Publication, New York. Biswas, A., Gaiser, B.K., Jepson, M.A., Lead, J.R., Rosenkranz, P., Stone, V., 2011. Effects of silver and Cerium dioxide micro- and nano-sized particles on Daphni. J. Environ. Monit. 5, 1227–1235. Nalabotu, S.K., Kolli, M.B., Triest, W.E., Ma, J.Y., Manne, N.D.P.K., 2011. Intratracheal instillation of cerium oxide nanoparticles induces hepatic toxicity. Nanomedicine 6, 2327–2335.
Relevant Websites http://www.healtheffects.org – Evaluation of Human Health Risk from Cerium Added to Diesel Fuel. Health Effects Institute Communication 9 (August 2001). http://www.chemicool.com/elements/cerium.html – "Cerium." Chemicool Periodic Table. Chemicool.com. (June 2011)