The following information was generated from the 

Hazardous Substances Data Bank (HSDB), 

a database of the National Library of Medicine's TOXNET system 

(http://toxnet.nlm.nih.gov) on October 27, 2009. 

Query: The chemical name antimony was identified. 

The following terms were added from ChemIDplus: 

stibium 

antymon 

antimony black 

CAS Registry Number: 7440-36-0 

1 

NAME: ANTIMONY, ELEMENTAL 

RN: 7440-36-0 

NOTE: 

 This record contains information for antimony in its zero valence state 

 only. For general toxicity and environmental fate of antimony ions and 

 antimony compounds, refer to the ANTIMONY COMPOUNDS record; for 

 compound-specific information, to the appropriate individual records, 

 e.g., antimony trioxide, antimony pentachloride, etc. 

HUMAN HEALTH EFFECTS: 

HUMAN TOXICITY EXCERPTS: 

 Chronic effects due to antimony are alterations of the ECG, especially 

 T-wave abnormalities, myocardial changes, pneumoconiosis, but also 

 pneumonitis, tracheitis, laryngitis, bronchitis, pustular skin eruptions 

 called antimony spots, and contact allergy to the metal. [Seiler, H.G., H. 

 Sigel and A. Sigel (eds.). Handbook on the Toxicity of Inorganic 

 Compounds. New York, NY: Marcel Dekker, Inc. 1988., p. 71] **PEER 

 REVIEWED** 

 ... ANTIMONY DUST IN FOUNDRY WAS IMPORTANT CAUSE OF GASTROINTESTINAL 

 SYMPTOMS ... /IN/ EXPOSED WORKERS. ... DYSPNEA, HEADACHE, VOMITING, 

 CONJUNCTIVITIS ... BLOODY PURULENT DISCHARGE FROM NOSE ... . [Hamilton, 

 A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: 

 Publishing Sciences Group, Inc., 1974., p. 27] **PEER REVIEWED** 

 ... ANTIMONY POISONING AMONG SMELTER WORKERS ... ANTIMONY WAS ... 

 PREDOMINANT CONTAMINANT /IN ATMOSPHERE/ ... LEVELS ... FROM 4.69-11.81 

 MG/CU M ... DERMATITIS & RHINITIS ... INFLAMMATION OF UPPER & 

 LOWER RESP TRACT INCL PNEUMONITIS ... GASTRITIS ... SEPTAL PERFORATIONS. 

 [Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: 

 Toxicology. 2nd ed. New York: Interscience Publishers, 1963., p. 997] 

 **PEER REVIEWED** 

 DERMAL EFFECTS, KNOWN AS ANTIMONY SPOTS, HAVE BEEN KNOWN FOR YEARS, BUT 

 PNEUMOCONIOSIS HAS COME TO BE KNOWN ONLY RELATIVELY RECENTLY. ... ANTIMONY 

 SPOTS IS A RASH CONSISTING OF PAPULES AND PUSTULES AROUND SWEAT AND 

 SEBACEOUS GLANDS, RESEMBLING THE PUSTULES OF CHICKEN POX. IT AFFECTS 

 FOREARMS, THIGHS, AND SITES WHERE FLEXING AND CHAFING OF CLOTHES OCCUR, 

 AND IS MORE COMMON IN HOT WEATHER. ... PNEUMOCONIOSIS ... WAS POSITIVELY 

 DEMONSTRATED IN THREE OF 28, AND RATED "SUSPICIOUS" IN FIVE ANTIMONY 

 SMELTER AND ORE PROCESSORS AGED 25 TO 61 YEARS, BUT ... NO CONSISTENT 

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 PATTERNS OF FUNCTIONAL ABNORMALITIES WERE FOUND. ... PREVIOUS TO THE 

 TESTS, ANTIMONY AIR CONCENTRATIONS RANGED FROM 0.08 TO 138 MG/CU M WITH 

 PARTICLES LESS THAN 3 UM IN DIAMETER. ... OF A GROUP OF 40 FRENCH WORKERS 

 SIMILARLY EMPLOYED FOR 6 TO 40 YEARS, 10 WERE CONSIDERED TO HAVE 

 PNEUMOCONIOSIS AT ANTIMONY AIR CONCENTRATIONS CONSIDERABLY LOWER (0.3 TO 

 14.7 MG/CU M). [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial 

 Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th 

 ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 1906-8] 

 **PEER REVIEWED** 

 Women working in an antimony metallurgical plant were compared to a 

 similar group of women not exposed to antimony. The exposed group had 

 higher incidences of spontaneous abortions (12.5 vs 4.1%), premature 

 births (3.4 vs 1.2%), and gynecological problems (77.5 vs 56%). The 

 gynecological problems included menstrual cycle disorders (61.2 vs 35.7%), 

 inflammatory disease (30.4 vs 55.3%) and other reproductive problems (8.4% 

 of exposed women). These women were exposed to unspecified amounts of 

 antimony trioxide, metallic antimony, and antimony pentasulfides. Children 

 born to these exposed women weighed significantly less after 1 year when 

 compared with children born to nonexposed women; there were no 

 statistically significant differences in weights at birth of the two sets 

 of children. [Belyaeva AP; Gig Truda Prof Zabole 11:32 (1964) as cited in 

 Health Effects Assessment for Antimony and Compounds p.13-14 (1987) EPA 

 600/8-88/018] **PEER REVIEWED** 

 ANTIMONY AND ITS COMPOUNDS REPORTED TO CAUSE DERMATITIS, KERATITIS, 

 CONJUNCTIVITIS, & NASAL SEPTAL ULCERATION BY CONTACT, FUMES OR DUST. 

 [Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, 

 Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 

 1996., p. 118] **PEER REVIEWED** 

 DUST ENCOUNTERED IN ANTIMONY MINING MAY CONTAIN FREE SILICA & CASES OF 

 PNEUMOCONIOSIS TERMED "SILICO-ANTIMONIOSIS" HAVE BEEN REPORTED AMONG 

 ANTIMONY MINERS. DURING PROCESSING, ANTIMONY ORE ... IS CONVERTED INTO 

 FINE DUST ... LEADING TO HIGH ATMOSPHERIC CONCN OF FINE DUST. 

 [International Labour Office. Encyclopedia of Occupational Health and 

 Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 

 1983., p. 177] **PEER REVIEWED** 

 Antimony dust has produced pneumoconiosis in antimony miners (usually a 

 mixed-dust lesion such as silicoantimoniosis) and in men working with 

 stibnite. Fine, nodular opacities may be seen, and ventilatory function 

 remains normal. Other findings may include rhinitis, conjunctivitis, 

 bronchitis, dermatitis, and nasal septal perforation. Exposure to metal 

 fumes and oxidized metal powder over many years has been associated with 

 chronic obstructive pulmonary disease. [Rom, W.N. (ed.). Environmental and 

 Occupational Medicine. 2nd ed. Boston, MA: Little, Brown and Company, 

 1992., p. 480] **PEER REVIEWED** 

MEDICAL SURVEILLANCE: 

 Periodic chest X-ray, pulmonary function testing, and electrocardiogram 

 required. [NIOSH/CDC. NIOSH Recommendations for Occupational Safety and 

 Health Standards 1988, Aug. 1988. (Suppl. to Morbidity and Mortality Wkly. 

 Vol. 37 No. 5-7, Aug. 26, 1988). Atlanta, GA: National Institute for 

 Occupational Safety and Health, CDC, 1988., p. 5] **PEER REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 LEAD-ANTIMONY ALLOY IS USED LARGELY IN MANUFACTURE OF STORAGE BATTERY 

 GRIDS, PEWTER & BRITANNIA METAL, PRINTER'S TYPE, LEAD SHOT, LEAD 

 ELECTRODES AND BEARING METALS. IN MANY OF THESE PROCESSES THE GREATEST 

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 EXPOSURE IS TO ANTIMONY METAL DUST AND FUME. [Browning, E. Toxicity of 

 Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 

 24] **PEER REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 LEAD-ANTIMONY ALLOY IS USED LARGELY IN MANUFACTURE OF STORAGE BATTERY 

 GRIDS, PEWTER & BRITANNIA METAL, PRINTER'S TYPE, LEAD SHOT, LEAD 

 ELECTRODES AND BEARING METALS. IN MANY OF THESE PROCESSES THE GREATEST 

 EXPOSURE IS TO ANTIMONY METAL DUST AND FUME. [Browning, E. Toxicity of 

 Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 

 24] **PEER REVIEWED** 

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The following information was generated from the 

Hazardous Substances Data Bank (HSDB), 

a database of the National Library of Medicine's TOXNET system 

(http://toxnet.nlm.nih.gov) on October 27, 2009. 

Query: The chemical name arsenic was identified. 

The following terms were added from ChemIDplus: 

metallic arsenic 

colloidal arsenic 

arsenic black 

CAS Registry Number: 7440-38-2 

1 

NAME: ARSENIC, ELEMENTAL 

RN: 7440-38-2 

NOTE: 

 This record contains information for arsenic in its zero valence state 

 only. For general toxicity and environmental fate of arsenic ions and 

 arsenic compounds, refer to the ARSENIC COMPOUNDS record; for compound 

 specific information, refer to the appropriate individual records, e.g., 

 arsenic trichloride, diethyl arsine, etc. 

HUMAN HEALTH EFFECTS: 

EVIDENCE FOR CARCINOGENICITY: 

 CLASSIFICATION: A; human carcinogen. BASIS FOR CLASSIFICATION: Based on 

 sufficient evidence from human data. An increased lung cancer mortality 

 was observed in multiple human populations exposed primarily through 

 inhalation. Also, increased mortality from multiple internal organ cancers 

 (liver, kidney, lung, and bladder) and an increased incidence of skin 

 cancer were observed in populations consuming drinking water high in 

 inorganic arsenic. HUMAN CARCINOGENICITY DATA: Sufficient. ANIMAL 

 CARCINOGENICITY DATA: Inadequate. /Based on former classification system/ 

 [U.S. Environmental Protection Agency's Integrated Risk Information System 

 (IRIS) on Arsenic, inorganic (7440-38-2) Available from: 

 http://www.epa.gov/ngispgm3/iris on the Substance File List as of March 

 15, 2000] **QC REVIEWED** 

 A1: Confirmed human carcinogen. /Arsenic and inorganic compounds, as As/ 

 [American Conference of Governmental Industrial Hygienists. Threshold 

 Limit Values of Chemical Substances and Biological Exposure Indices, 

 ACGIH, Cincinnati, OH 2009, p. 12] **QC REVIEWED** 

 Evaluation: There is sufficient evidence in humans that arsenic in 

 drinking-water causes cancers of the urinary bladder, lung and skin ... 

 Overall evaluation: Arsenic in drinking-water is carcinogenic to humans 

 (Group 1). /Arsenic in drinking-water/ [IARC. Monographs on the Evaluation 

 of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health 

 Organization, International Agency for Research on Cancer, 1972-PRESENT. 

 (Multivolume work)., p. V84 (2004)] **QC REVIEWED** 

 Arsenic compounds, inorganic: known to be a human carcinogen. [U.S. 

 Department of Health & Human Services/National Toxicology Program; 

 Eleventh Report on Carcinogens: Arsenic Compounds, Inorganic (January 

 2005). Available from, as of July 24, 2009: 

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 http://ntp.niehs.nih.gov/ntp/roc/toc11.html ] **QC REVIEWED** 

 Classification of carcinogenicity: 1) evidence in humans: sufficient; 2) 

 evidence in animals: limited. Overall summary evaluation of carcinogenic 

 risk to humans is Group 1: Carcinogenic to humans. NOTE: This evaluation 

 applies to the group of chemicals as a whole and not necessarily to all 

 individual chemicals within the group. /Arsenic and arsenic compounds/ 

 [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals 

 to Man. Geneva: World Health Organization, International Agency for 

 Research on Cancer, 1972-PRESENT. (Multivolume work)., p. S7 57 (1987)] 

 **QC REVIEWED** 

HUMAN TOXICITY EXCERPTS: 

 Among smelter workers exposed to a mixture of metals including arsenic, 

 the frequency of congenital malformations did not differ from non-exposed 

 populations. However, mean birth wt were reported to be decr in offspring 

 of female employees of the smelter. [Friberg, L., Nordberg, G.F., Kessler, 

 E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. 

 Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986., p. V1 

 414] **PEER REVIEWED** 

 The low toxicity of elemental arsenic is attributed to its virtual 

 insolubility in water or in body fluids. [USEPA; Ambient Water Quality 

 Criteria Doc: Arsenic p.A-1 (1980) EPA 440/5-80-021] **PEER REVIEWED** 

MEDICAL SURVEILLANCE: 

 The urinary excretion, in mg/L, of elements that are freely eliminated by 

 this route, such as ... arsenic, is at most 2.5-5 times the occupation 

 exposure in mg/cu m of air /SRP: for an 8 hour day/. It is apparent that 

 biological monitoring for arsenic by urinalysis would be of limited value 

 in determining whether or not the NIOSH recommended standard ... was being 

 met or exceeded. [American Conference of Governmental Industrial 

 Hygienists, Inc. Documentation of the Threshold Limit Values and 

 Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: 

 ACGIH, 1991., p. 83] **PEER REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 Ceramic artists can be exposed to many hazardous materials, generally 

 related to dry clays, glazes and kiln use. Glazes can contain lead, 

 antimony, arsenic, barium, beryllium, boron, chromium, cobalt, cadmium, 

 copper, vanadium and other materials. ... [Hart C; J Environ Health 49 

 (5): 282-6 (1987)] **PEER REVIEWED** 

 Heavy metals such as lead, arsenic, antimony, cadmium, chromium, cobalt, 

 manganese, and mercury ... used as color pigments in paints can be 

 ingested by contamination of hands, fingernails, food, cups, cigarettes 

 and by holding paint brushes in the mouth. [Hart C; J Environ Health 49 

 (5): 282 (1987)] **PEER REVIEWED** 

MINIMUM FATAL DOSE LEVEL: 

 Fatal human dose 70-180 mg depending on weight. Estimated lethal dose for 

 a 70 kg human as As (III). [NIH/EPA; OHM/TADS (1985)] **PEER REVIEWED** 

EVIDENCE FOR CARCINOGENICITY: 

 CLASSIFICATION: A; human carcinogen. BASIS FOR CLASSIFICATION: Based on 

 sufficient evidence from human data. An increased lung cancer mortality 

 was observed in multiple human populations exposed primarily through 

 inhalation. Also, increased mortality from multiple internal organ cancers 

 (liver, kidney, lung, and bladder) and an increased incidence of skin 

 cancer were observed in populations consuming drinking water high in 

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 inorganic arsenic. HUMAN CARCINOGENICITY DATA: Sufficient. ANIMAL 

 CARCINOGENICITY DATA: Inadequate. /Based on former classification system/ 

 [U.S. Environmental Protection Agency's Integrated Risk Information System 

 (IRIS) on Arsenic, inorganic (7440-38-2) Available from: 

 http://www.epa.gov/ngispgm3/iris on the Substance File List as of March 

 15, 2000] **QC REVIEWED** 

 A1: Confirmed human carcinogen. /Arsenic and inorganic compounds, as As/ 

 [American Conference of Governmental Industrial Hygienists. Threshold 

 Limit Values of Chemical Substances and Biological Exposure Indices, 

 ACGIH, Cincinnati, OH 2009, p. 12] **QC REVIEWED** 

 Evaluation: There is sufficient evidence in humans that arsenic in 

 drinking-water causes cancers of the urinary bladder, lung and skin ... 

 Overall evaluation: Arsenic in drinking-water is carcinogenic to humans 

 (Group 1). /Arsenic in drinking-water/ [IARC. Monographs on the Evaluation 

 of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health 

 Organization, International Agency for Research on Cancer, 1972-PRESENT. 

 (Multivolume work)., p. V84 (2004)] **QC REVIEWED** 

 Arsenic compounds, inorganic: known to be a human carcinogen. [U.S. 

 Department of Health & Human Services/National Toxicology Program; 

 Eleventh Report on Carcinogens: Arsenic Compounds, Inorganic (January 

 2005). Available from, as of July 24, 2009: 

 http://ntp.niehs.nih.gov/ntp/roc/toc11.html ] **QC REVIEWED** 

 Classification of carcinogenicity: 1) evidence in humans: sufficient; 2) 

 evidence in animals: limited. Overall summary evaluation of carcinogenic 

 risk to humans is Group 1: Carcinogenic to humans. NOTE: This evaluation 

 applies to the group of chemicals as a whole and not necessarily to all 

 individual chemicals within the group. /Arsenic and arsenic compounds/ 

 [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals 

 to Man. Geneva: World Health Organization, International Agency for 

 Research on Cancer, 1972-PRESENT. (Multivolume work)., p. S7 57 (1987)] 

 **QC REVIEWED** 

MINIMUM FATAL DOSE LEVEL: 

 Fatal human dose 70-180 mg depending on weight. Estimated lethal dose for 

 a 70 kg human as As (III). [NIH/EPA; OHM/TADS (1985)] **PEER REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 Ceramic artists can be exposed to many hazardous materials, generally 

 related to dry clays, glazes and kiln use. Glazes can contain lead, 

 antimony, arsenic, barium, beryllium, boron, chromium, cobalt, cadmium, 

 copper, vanadium and other materials. ... [Hart C; J Environ Health 49 

 (5): 282-6 (1987)] **PEER REVIEWED** 

 Heavy metals such as lead, arsenic, antimony, cadmium, chromium, cobalt, 

 manganese, and mercury ... used as color pigments in paints can be 

 ingested by contamination of hands, fingernails, food, cups, cigarettes 

 and by holding paint brushes in the mouth. [Hart C; J Environ Health 49 

 (5): 282 (1987)] **PEER REVIEWED** 

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The following information was generated from the 

Hazardous Substances Data Bank (HSDB), 

a database of the National Library of Medicine's TOXNET system 

(http://toxnet.nlm.nih.gov) on October 27, 2009. 

Query: The chemical name barium was identified. 

The following terms were added from ChemIDplus: 

baryum 

bario 

CAS Registry Number: 7440-39-3 

1 

NAME: BARIUM, ELEMENTAL 

RN: 7440-39-3 

NOTE: 

 This record contains information for barium in its zero valence state 

 only. For general toxicology and environmental fate of barium ion and 

 barium compounds, refer to the BARIUM COMPOUNDS record; for 

 compound-specific information, refer to the appropriate individual 

 records, e.g., barium sulfate, barium chloride, etc. 

HUMAN HEALTH EFFECTS: 

TOXICITY SUMMARY: 

 IDENTIFICATION: Barium is a yellowish white soft metal that is strongly 

 electropositive. In nature barium occurs in a combined state, the 

 principal forms being barite (barium sulfate) and witherite (barium 

 carbonate). Barium is also present in small quantities in igneous rocks 

 such as feldspar and micas. It may also be found as a natural component of 

 fossil fuel and is present in the air, water and soil. HUMAN EXPOSURE: 

 Exposure to barium can occur through the air, water or food. Another souce 

 of barium is nuclear fallout. The average person accumulates 91% of barium 

 in bones. Trace quantities are found in various tissues such as the aorta, 

 brain, heart, kidney, spleen, pancreas and lung. Total barium in human 

 beings tends to increase with age and the levels in the body depend on the 

 geographical location of the individual. Barium has also been found in all 

 samples of stillborn babies, suggesting it can cross the placenta. Inhaled 

 barium can be absorbed through the lung or directly from the nasal 

 membrane into the blood. Barium is eliminated in the urine and feces, the 

 rates varying with the route of administration. Within 24 hr approximately 

 20% of the barium dose, injected into humans was eliminated in the feces 

 and approxinately 5% in the urine. Plasma barium is almost eliminated from 

 the blood stream within 24 hr. ANIMAL/PLANT STUDIES: In general, barium 

 does not accumulate in common plants in sufficient quantities to be toxic 

 to animals. Large quantities of barium (as high as 1260 mg/kg) accumulated 

 in legumes, alfalfa and soybeans. The elimination of ingested barium in 

 animals occurs mainly in the feces rather than in the urine. An estimated 

 of the biological half-life for barium in the rat is 90-120 days. The 

 acute effects of barium ingestion in animals includes salivation, nausea, 

 diarrhea, tachycardia, hypokalaemia, twitching, flacid paralysis of 

 skeletal muscle, respiratory muscle paralysis and ventricular fibrillation 

 may lead to death. Various studies have demonstrated the detremental 

 effect of barium upon ventricular automaticity and pacemaker current in 

 the heart. IV barium injections to anesthetized dogs indicated that these 

 acute effects were due to prompt and substantial hypokalemia. Barium 

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 causes mild skin and eye irritation. No conclusive association was found 

 between the level of barium in the drinking water and the incidence of 

 congenital malformations. There is no evidence that barium is 

 carcinogenic. Rats given 10 or 100 mg barium/l in their drinking water for 

 16 months experienced hypertension, but at a level of 1 mg/l did not 

 induce any blood pressure changes. Analysis of myocardial function at 16 

 months (100 mg barium/l) revealed significantly altered cardiac 

 contractility and excitability, myocardial metabolic disturbances and 

 hypersensitivity of the cardiovascular system to sodium pentobarbital. 

 Barium posesses chemical and physiological properties that allow it to 

 compete with and replace calcium, particularly those relating to the 

 release of adrenal catecholamines and neurotransmitters such as 

 acetylcholine and norepinephrine. Barium affects the development of 

 germinating bacterial spores and has a variety of specific effects on 

 different microorganisms including the inhibition of cellular processes. 

 Little information is available on the effects of barium on aquatic 

 organisms. There were no effects on survival of fish following exposure 

 for 30 days. However, in a 21 day study, impairment of reproduction and 

 reduction in growth in daphnids. Marine plants as well as invertebrates 

 may actively accumulate barium from sea water. [Environmental Health 

 Criteria 107 Barium. pp.13-19 (1990) by the International Programme on 

 Chemical Safety (IPCS) under the joint sponsorship of the United Nations 

 Environment Programme, the International Labour Organisation and the World 

 Health Organization.] **QC REVIEWED** 

EVIDENCE FOR CARCINOGENICITY: 

 WEIGHT OF EVIDENCE CHARACTERIZATION: Under EPA's 1986 Guidelines for 

 Carcinogen Risk Assessment, barium would be classified as Group D, not 

 classifiable as to human carcinogenicity. Although adequate chronic oral 

 exposure studies in rats and mice have not demonstrated carcinogenic 

 effects, the lack of adequate inhalation studies precludes assessing the 

 carcinogenic potential of inhaled barium. Under the Proposed Guidelines 

 for Carcinogenic Risk Assessment, barium is considered not likely to be 

 carcinogenic to humans following oral exposure and its carcinogenic 

 potential cannot be determined following inhalation exposure. Basis - Oral 

 exposure studies in rats and mice ... did not find significant increases 

 in tumor incidence following chronic exposure. In the 1994 NTP rat study 

 /National Toxicology Program Technical Report Series #432 on Barium 

 Chloride Dihydrate (10326-27-9)/, statistically significant negative 

 trends in the incidence of leukemia, adrenal tumors, and mammary gland 

 tumors were observed. The design of the rat and mouse NTP studies was 

 adequate to assess carcinogenicity. These studies used an adequate number 

 of animals per group, exposed animals for 2 years, tested several dosage 

 levels, and examined an extensive number of tissues. The inhalation 

 exposure and intratracheal studies ... are inadequate for subchronic 

 exposure carcinogenicity evaluation because of several deficiencies in the 

 design and reporting ... HUMAN CARCINOGENICITY DATA: Inadequate. ANIMAL 

 CARCINOGENICITY DATA: Oral Exposure - Sufficient; Inhalation Studies - 

 Inadequate. [U.S. Environmental Protection Agency's Integrated Risk 

 Information System (IRIS) for Barium and compounds (7440-39-3) Available 

 from: http://www.epa.gov/ngispgm3/iris on the Substance File List as of 

 August 10, 1998] **PEER REVIEWED** 

 A4; Not classifiable as a human carcinogen. /Barium and soluble compounds, 

 as Ba/ [American Conference of Governmental Industrial Hygienists TLVs and 

 BEIs. Threshold Limit Values for Chemical Substances and Physical Agents 

 and Biological Exposure Indices. Cincinnati, OH, 2008, p. 13] **QC 

 REVIEWED** 

HUMAN TOXICITY EXCERPTS: 

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 The rapid onset of reflex paralysis was reported in a chrome-plating 

 worker following the inhalation of barium powder. Complete recovery 

 occurred during the 5-day period that followed exposure. [WHO; Environ 

 Health Criteria 107: Barium p.90 (1990)] **PEER REVIEWED** 

 Several hundred cases of acute or subacute barium poisoning occurred in 

 the Kiating district of China, where table salt contained a large amt of 

 barium (up to 26%). The victims suffered sudden attacks of paralysis, 

 ranging from mild to severe, paraesthesia, and cardiac symptoms, but 

 recovery was usually rapid ... . [WHO; Environ Health Criteria 107: Barium 

 p.90 (1990)] **PEER REVIEWED** 

 BARIUM IS NOT CONSIDERED TO BE AN INDUSTRIAL HEALTH HAZARD ... . 

 [Venugopal, B. and T.D. Luckey. Metal Toxicity in Mammals, 2. New York: 

 Plenum Press, 1978., p. 63] **PEER REVIEWED** 

 The prolonged contact of barium containing contraceptive devices with 

 cervical cells presented a potential cancer risk in susceptible 

 individuals. [Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra 

 Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 926] 

 **PEER REVIEWED** 

MEDICAL SURVEILLANCE: 

 Consideration should be given to the skin, eye, heart, & lung in any 

 placement or periodic examination. [Sittig, M. Handbook of Toxic and 

 Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes 

 Data Corporation, 1985., p. 105] **PEER REVIEWED** 

 ... Individuals with pulmonary diseases /should be protected from 

 exposure/. [ITII. Toxic and Hazarous Industrial Chemicals Safety Manual. 

 Tokyo, Japan: The International Technical Information Institute, 1982., p. 

 57] **PEER REVIEWED** 

POPULATIONS AT SPECIAL RISK: 

 ... Those individuals with pulmonary diseases. [ITII. Toxic and Hazarous 

 Industrial Chemicals Safety Manual. Tokyo, Japan: The International 

 Technical Information Institute, 1982., p. 57] **PEER REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 Ingestion or inhalation of dust or fume, skin or eye contact. [Sittig, M. 

 Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. 

 Park Ridge, NJ: Noyes Data Corporation, 1985., p. 105] **PEER REVIEWED** 

 

TOXICITY SUMMARY: 

 IDENTIFICATION: Barium is a yellowish white soft metal that is strongly 

 electropositive. In nature barium occurs in a combined state, the 

 principal forms being barite (barium sulfate) and witherite (barium 

 carbonate). Barium is also present in small quantities in igneous rocks 

 such as feldspar and micas. It may also be found as a natural component of 

 fossil fuel and is present in the air, water and soil. HUMAN EXPOSURE: 

 Exposure to barium can occur through the air, water or food. Another souce 

 of barium is nuclear fallout. The average person accumulates 91% of barium 

 in bones. Trace quantities are found in various tissues such as the aorta, 

 brain, heart, kidney, spleen, pancreas and lung. Total barium in human 

 beings tends to increase with age and the levels in the body depend on the 

 geographical location of the individual. Barium has also been found in all 

 samples of stillborn babies, suggesting it can cross the placenta. Inhaled 

 barium can be absorbed through the lung or directly from the nasal 

 membrane into the blood. Barium is eliminated in the urine and feces, the 

 rates varying with the route of administration. Within 24 hr approximately 

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 20% of the barium dose, injected into humans was eliminated in the feces 

 and approxinately 5% in the urine. Plasma barium is almost eliminated from 

 the blood stream within 24 hr. ANIMAL/PLANT STUDIES: In general, barium 

 does not accumulate in common plants in sufficient quantities to be toxic 

 to animals. Large quantities of barium (as high as 1260 mg/kg) accumulated 

 in legumes, alfalfa and soybeans. The elimination of ingested barium in 

 animals occurs mainly in the feces rather than in the urine. An estimated 

 of the biological half-life for barium in the rat is 90-120 days. The 

 acute effects of barium ingestion in animals includes salivation, nausea, 

 diarrhea, tachycardia, hypokalaemia, twitching, flacid paralysis of 

 skeletal muscle, respiratory muscle paralysis and ventricular fibrillation 

 may lead to death. Various studies have demonstrated the detremental 

 effect of barium upon ventricular automaticity and pacemaker current in 

 the heart. IV barium injections to anesthetized dogs indicated that these 

 acute effects were due to prompt and substantial hypokalemia. Barium 

 causes mild skin and eye irritation. No conclusive association was found 

 between the level of barium in the drinking water and the incidence of 

 congenital malformations. There is no evidence that barium is 

 carcinogenic. Rats given 10 or 100 mg barium/l in their drinking water for 

 16 months experienced hypertension, but at a level of 1 mg/l did not 

 induce any blood pressure changes. Analysis of myocardial function at 16 

 months (100 mg barium/l) revealed significantly altered cardiac 

 contractility and excitability, myocardial metabolic disturbances and 

 hypersensitivity of the cardiovascular system to sodium pentobarbital. 

 Barium posesses chemical and physiological properties that allow it to 

 compete with and replace calcium, particularly those relating to the 

 release of adrenal catecholamines and neurotransmitters such as 

 acetylcholine and norepinephrine. Barium affects the development of 

 germinating bacterial spores and has a variety of specific effects on 

 different microorganisms including the inhibition of cellular processes. 

 Little information is available on the effects of barium on aquatic 

 organisms. There were no effects on survival of fish following exposure 

 for 30 days. However, in a 21 day study, impairment of reproduction and 

 reduction in growth in daphnids. Marine plants as well as invertebrates 

 may actively accumulate barium from sea water. [Environmental Health 

 Criteria 107 Barium. pp.13-19 (1990) by the International Programme on 

 Chemical Safety (IPCS) under the joint sponsorship of the United Nations 

 Environment Programme, the International Labour Organisation and the World 

 Health Organization.] **QC REVIEWED** 

EVIDENCE FOR CARCINOGENICITY: 

 WEIGHT OF EVIDENCE CHARACTERIZATION: Under EPA's 1986 Guidelines for 

 Carcinogen Risk Assessment, barium would be classified as Group D, not 

 classifiable as to human carcinogenicity. Although adequate chronic oral 

 exposure studies in rats and mice have not demonstrated carcinogenic 

 effects, the lack of adequate inhalation studies precludes assessing the 

 carcinogenic potential of inhaled barium. Under the Proposed Guidelines 

 for Carcinogenic Risk Assessment, barium is considered not likely to be 

 carcinogenic to humans following oral exposure and its carcinogenic 

 potential cannot be determined following inhalation exposure. Basis - Oral 

 exposure studies in rats and mice ... did not find significant increases 

 in tumor incidence following chronic exposure. In the 1994 NTP rat study 

 /National Toxicology Program Technical Report Series #432 on Barium 

 Chloride Dihydrate (10326-27-9)/, statistically significant negative 

 trends in the incidence of leukemia, adrenal tumors, and mammary gland 

 tumors were observed. The design of the rat and mouse NTP studies was 

 adequate to assess carcinogenicity. These studies used an adequate number 

 of animals per group, exposed animals for 2 years, tested several dosage 

 levels, and examined an extensive number of tissues. The inhalation 

 exposure and intratracheal studies ... are inadequate for subchronic 

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 exposure carcinogenicity evaluation because of several deficiencies in the 

 design and reporting ... HUMAN CARCINOGENICITY DATA: Inadequate. ANIMAL 

 CARCINOGENICITY DATA: Oral Exposure - Sufficient; Inhalation Studies - 

 Inadequate. [U.S. Environmental Protection Agency's Integrated Risk 

 Information System (IRIS) for Barium and compounds (7440-39-3) Available 

 from: http://www.epa.gov/ngispgm3/iris on the Substance File List as of 

 August 10, 1998] **PEER REVIEWED** 

 A4; Not classifiable as a human carcinogen. /Barium and soluble compounds, 

 as Ba/ [American Conference of Governmental Industrial Hygienists TLVs and 

 BEIs. Threshold Limit Values for Chemical Substances and Physical Agents 

 and Biological Exposure Indices. Cincinnati, OH, 2008, p. 13] **QC 

 REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 Ingestion or inhalation of dust or fume, skin or eye contact. [Sittig, M. 

 Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. 

 Park Ridge, NJ: Noyes Data Corporation, 1985., p. 105] **PEER REVIEWED** 

 

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The following information was generated from the 

Hazardous Substances Data Bank (HSDB), 

a database of the National Library of Medicine's TOXNET system 

(http://toxnet.nlm.nih.gov) on October 27, 2009. 

Query: The chemical name beryllium was identified. 

The following terms were added from ChemIDplus: 

glucinum 

glucinium 

CAS Registry Number: 7440-41-7 

1 

NAME: BERYLLIUM, ELEMENTAL 

RN: 7440-41-7 

NOTE: 

 This record contains information for beryllium in its zero valence state 

 only. For general information on the toxicity and environmental fate of 

 beryllium ion and beryllium compounds, refer to the BERYLLIUM COMPOUNDS 

 record; for compound-specific information, refer to the appropriate 

 individual records, e.g., beryllium oxide, beryllium sulfate, etc. 

HUMAN HEALTH EFFECTS: 

TOXICITY SUMMARY: 

 Exposure of people to relatively high concentrations of beryllium (greater 

 than 100 ug cu m) causes acute beryllium disease, characterized by 

 chemical pneumonitis. ... Some people inhaling low concentrations of 

 beryllium develop chronic beryllium disease, a granulomatous lung disease 

 characterized by dyspnea, cough, reduced pulmonary function, and a variety 

 of other symptoms, including weight loss. ... The lack of a dose-response 

 relationship between the extent of exposure and development of the 

 disease, long latency period between exposure and onset, and the low 

 incidence among beryllium-exposed individuals suggests that the disease is 

 immune mediated. ... Occupational risk associated with exposure to 

 beryllium-containing alloys has been documented for individuals exposed to 

 beryllium-copper and beryllium-nickel alloys. Beryllium is a suspected 

 human carcinogen, based on results of animal data. Epidemiologic evidence 

 relating beryllium exposure to cancer in humans is inadequate to 

 demonstrate or refute that beryllium is carcinogenic in humans, and the 

 International Agency for Research on Cancer lists the evidence for 

 beryllium induced carcinogenicity in humans as "limited". ... The 

 pulmonary effects of inhaled beryllium have also been evaluated in a 

 variety of laboratory animal species. ... monkeys exposed to relatively 

 high concentrations of beryllium compounds developed symptoms and 

 histopathological findings consistent with acute beryllium disease. ... 

 Granulomatous lung disease has also been produced in guinea pigs exposed 

 to beryllium compounds by inhalation or by intratracheal instillation. ... 

 Repeated inhalation of beryllium-containing materials, including soluble 

 beryllium compounds by various strains of laboratory rats has resulted in 

 development of inflammatory and proliferative changes, granulomatous lung 

 changes, and the development of lung tumors. Although beryllium- exposed 

 rats have developed various degrees of granulomatous lung disease, none 

 have developed immunopathological responses in lung or beryllium 

 hypersensitivity. ... studies have shown that several strains of mice 

 inhaling beryllium develop pulmonary lesions with features consistent with 

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 chronic beryllium disease. Lung lesions consisted of infiltration of 

 lymphocytes into the lung interstitium, development of microgranulomas 

 consisting of T lymphocytes and macrophages, and the presence of some 

 pulmonary fibrosis. Under certain exposure conditions, increased numbers 

 of lymphocytes were recovered in bronchoalveolar lavage fluid from exposed 

 animals. [Chang, L.W. (ed.). Toxicology of Metals. Boca Raton, FL: Lewis 

 Publishers, 1996, p. 929-30] **PEER REVIEWED** 

EVIDENCE FOR CARCINOGENICITY: 

 WEIGHT OF EVIDENCE CHARACTERIZATION: B1; probable human carcinogen. Based 

 on the limited evidence of carcinogenicity in humans exposed to airborne 

 beryllium (lung cancer) and sufficient evidence of carcinogenicity in 

 animals (lung cancer in rats and monkeys inhaling beryllium, lung tumors 

 in rats exposed to beryllium via intratracheal instillation, and 

 osteosarcomas in rabbits and possibly mice receiving intravenous or 

 intramedullary injection), beryllium is reclassified from a B2 (inadequate 

 human data) to a B1 probable human carcinogen (limited human data) using 

 criteria of the 1986 Guidelines for Carcinogen Risk Assessment. Using the 

 proposed Guidelines for Carcinogen Risk Assessment, inhaled beryllium 

 would be characterized as a "likely" carcinogen in humans, and the human 

 carcinogenic potential of ingested beryllium cannot be determined. Studies 

 regarding the potential carcinogenicity of ingested beryllium to humans 

 were not available. Increases in lung cancer mortality have been observed 

 in cohort mortality studies of beryllium processing workers ... and in 

 studies of entrants on the BCR. No increases in other types of cancer were 

 found, but increases in deaths from nonmalignant respiratory disease were 

 also observed. Newer studies ... have been considered as the basis for a 

 dose-response assessment, but share a limitatiion ... lack of individul 

 exposure monitoring or job history data that would support a more 

 definitive exposure assessment. NIOSH has recently completed a lung cancer 

 case-control study nested within a cohort mortality study of beryllium 

 manufacturing workers at the Reading beryllium processing facility. The 

 study developed an exposure matrix and calculated airborne exposure 

 concentration and thus may provide the best available basis for a 

 quantitative cancer estimate. ... Chronic oral studies of the potential 

 carcinogenicity of beryllium in animals were conducted at dose levels 

 below the /Maximum Tolerated Dose/, and therefore are inadequate for the 

 assessment of carcinogenicity. Beryllium has been shown to induce lung 

 cancer in rats exposed to beryllium by both inhalation and intratracheal 

 instillation and in monkeys by inhalation. Osteosarcomas have been 

 produced in rabbits and possibly in mice by intravenous and intramedullary 

 injection using a variety of beryllium compounds and beryllium metal. No 

 tumors were produced by intracutaneous or percutaneous injections of 

 beryllium compounds. The majority of studies do not induce gene mutation 

 in bacterial assays with or without metabolic activation. Gene mutations 

 have been observed in mammalian cells cultured with beryllium chloride. 

 Culturing mammalian cells with beryllium chloride, beryllium sulfate, or 

 beryllium nitrate has resulted in clastogenic alterations. HUMAN 

 CARCINOGENICITY DATA: Limited. ANIMAL CARCINOGENICITY DATA: Sufficient. 

 [U.S. Environmental Protection Agency's Integrated Risk Information System 

 (IRIS) for Beryllium and compounds (7440-41-7) Available from: 

 http://www.epa.gov/ngispgm3/iris on the Substance File List as of March 

 15, 2000] **QC REVIEWED** 

 Evaluation: There is sufficient evidence in humans for the carcinogenicity 

 of beryllium and beryllium compounds. There is sufficient evidence in 

 experimental animals for the carcinogenicity of beryllium and beryllium 

 compounds. Overall evaluation: Beryllium and beryllium compounds are 

 carcinogenic to humans (Group 1). /Beryllium and beryllium compounds/ 

 [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals 

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 to Man. Geneva: World Health Organization, International Agency for 

 Research on Cancer, 1972-PRESENT. (Multivolume work)., p. 58 103 (1993)] 

 **PEER REVIEWED** 

 A1: Confirmed human carcinogen. /Beryllium and compounds, as Be/ [American 

 Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold 

 Limit Values for Chemical Substances and Physical Agents and Biological 

 Exposure Indices. Cincinnati, OH, 2008, p. 14] **QC REVIEWED** 

 Beryllium and Beryllium Compounds: known to be human carcinogens. 

 [DHHS/National Toxicology Program; Eleventh Report on Carcinogens: 

 Beryllium and Beryllium Compounds (January 2005). Available from, as of 

 July 31, 2009: 

 http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s022bery.pdf ] **QC 

 REVIEWED** 

HUMAN TOXICITY EXCERPTS: 

 THE ATTACK RATE FOR ACUTE PNEUMONITIS IN AN ORE REDUCTION OPERATION WITH 

 HIGHER EXPOSURES, WAS GREATER THAN 10% IN 1950, VERSUS 3% IN ALL 

 EMPLOYEES. SYMPTOMS FROM A FRANK EXPOSURE MAY APPEAR IN A FEW HR, & 

 RECOVERY IN FROM 1 TO 12 WK, RARELY WITH ANY RESIDUAL. THE TYPICAL SIGNS 

 OF CHEMICAL PNEUMONITIS APPEAR AS ANOREXIA, WEIGHT LOSS, WEAKNESS & 

 VARYING DEGREES OF CYANOSIS. THE PHYSICAL SIGNS INCLUDE LOWERED VITAL 

 CAPACITY, FINE TO COARSE SIBILANT RALES, & RAPID PULSE. X-RAY FINDINGS 

 ARE USUALLY A PERIBRONCHIAL HAZINESS & PUNCTATE INFILTRATION 

 THROUGHOUT THE LOWER LUNG FIELDS, OR IN SEVERE CASES, CONSOLIDATION. 

 [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and 

 Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley 

 Sons, 1981-1982., p. 1551] **PEER REVIEWED** 

 FUMES OF BERYLLIUM ... IN REFINING OR MFR PRODUCE METAL FUME FEVER, 

 CORYZA, BRONCHITIS. ... [Thienes, C., and T.J. Haley. Clinical Toxicology. 

 5th ed. Philadelphia: Lea and Febiger, 1972., p. 186] **PEER REVIEWED** 

 DEATH MAY RESULT FROM SHORT EXPOSURE TO VERY LOW CONCN OF THE ELEMENT 

 & ITS SALTS. CONTACT DERMATITIS, CHEMICAL CONJUNCTIVITIS, CORNEAL 

 BURNS, NON HEALING ULCERATION AT SITE OF INJURY, SUBCUTANEOUS NODULES MAY 

 OCCUR FOLLOWING EXPOSURE. ACUTE: PNEUMONITIS MAY RESULT FROM SINGLE 

 EXPOSURE TO BERYLLIUM & OCCASIONALLY IS FATAL. CHRONIC: PULMONARY 

 GRANULOMATOUS DISEASE MAY APPEAR IN 3 MO TO 15 YR, OFTEN AFTER SHORT 

 EXPOSURE TO LOW CONCN. UNCERTAINTY AS TO COMPLETE RECOVERY. DEATH RATE 

 ABOUT 25%. [The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 

 1983., p. 166] **PEER REVIEWED** 

 ... CHRONIC ... TOXICITY /CAUSED BY AIRBORNE DUST OF BERYLLIUM/ ... IN 

 SOME CASES YR AFTER CHRONIC INHALATION EXPOSURE ... HEART ENLARGEMENT 

 & CONGESTIVE HEART FAILURE ... ENLARGEMENT OF LIVER & SPLEEN ... 

 CELLULAR INFILTRATION IN INTERSTICES OF VARIOUS ORGANS & TISSUES, 

 & CALCIFIC INCLUSIONS IN CELLS & TISSUES. [Venugopal, B. and T.D. 

 Luckey. Metal Toxicity in Mammals, 2. New York: Plenum Press, 1978., p. 

 46] **PEER REVIEWED** 

 IN MEN OCCUPATIONALLY BERYLLIUM EXPOSED (LESS THAN 8 NG BE/CU M, 4-6 

 HR/DAY), BERYLLIUM CONCN IN BLOOD & URINE SHOWED MEAN INCR OF A FACTOR 

 OF 4 OVER CONTROL SUBJECTS. BERYLLIUM SPECIFIC STIMULATION OF THYMUS 

 DERIVED LYMPHOCYTES OF THE EXPOSED MEN WAS INCR SIGNIFICANTLY. [STIEFEL T 

 ET AL; ARCH TOXICOL 45 (2): 81 (1980)] **PEER REVIEWED** 

 ACUTE ... 1. INHALATION- ACUTE PNEUMONITIS ... CHEST PAIN, BRONCHIAL 

 SPASM, FEVER, DYSPNEA, CYANOSIS, COUGH, BLOOD TINGED SPUTUM, & NASAL 

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 DISCHARGE. RIGHT HEART FAILURE MAY OCCUR AS RESULT OF INCR PULMONARY 

 ARTERIAL RESISTANCE. ONSET OF SYMPTOMS ... 2-5 WK AFTER EXPOSURE OF 1-20 

 DAYS. ... 2. SKIN CONTACT ... ACUTE DERMATITIS FROM CONTACT WITH DUST 

 SIMULATES FIRST & SECOND DEGREE BURNS. 3. EYE CONTACT- DUST 

 CONTAMINATION CAUSES ACUTE CONJUNCTIVITIS WITH CORNEAL MACULAE & 

 DIFFUSE ERYTHEMA. [Dreisbach, R.H. Handbook of Poisoning. 12th ed. 

 Norwalk, CT: Appleton and Lange, 1987., p. 225] **PEER REVIEWED** 

 CHRONIC ... 1. INHALATION ... WT LOSS & MARKED DYSPNEA ... 3 MO TO 11 

 YR AFTER FIRST EXPOSURE. DISEASE ... DOWNHILL COURSE OR MAY BE MARKED BY 

 EXACERBATIONS & REMISSIONS. RIGHT HEART FAILURE ... FEVER IS VARIABLE. 

 ... 2. SKIN CONTACT- ECZEMATOUS DERMATITIS WITH MACULOPAPULAR, 

 ERYTHEMATOUS, VESICULAR RASH ... IN LARGE PERCENTAGE OF WORKERS EXPOSED TO 

 BERYLLIUM DUSTS. [Dreisbach, R.H. Handbook of Poisoning. 12th ed. Norwalk, 

 CT: Appleton and Lange, 1987., p. 225] **PEER REVIEWED** 

 ... 60 ... CASES OF CHRONIC BERYLLIUM DISEASE ... 18 PATIENTS HAD DIED: 13 

 FROM COR PULMONALE, 1 ... RESP INSUFFICIENCY, 1 ... CARDIAC ARREST, 1 ... 

 VIRUS PNEUMONIA, 1 ... RENAL INSUFFICIENCY & 1 ... UNSTATED CAUSE. 

 [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals 

 to Man. Geneva: World Health Organization, International Agency for 

 Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V1 25 (1972)] 

 **PEER REVIEWED** 

 IN CHRONIC SYSTEMIC BERYLLIUM POISONING ... THERE MAY BE CLINICAL 

 RESEMBLANCE TO BOECK'S SARCOID. RARELY THIS MAY BE ACCOMPANIED BY 

 CALCIFICATION OF CORNEA IN FORM OF BAND KERATOPATHY SUCH AS DEVELOPS IN 

 HYPERCALCEMIA ... [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, 

 IL: Charles C. Thomas Publisher, 1986., p. 145] **PEER REVIEWED** 

 OCULAR IRRITATION FROM INDUSTRIAL EXPOSURE ... CONJUNCTIVITIS ... SCARCELY 

 EVER INVOLVING CORNEA. HYPEREMIA OF CONJUNCTIVA & EDEMA OF LIDS ... 

 FROM EXPOSURE TO DUST OR DIRECT CONTAMINATION BY PARTICLES ... CAUSE 

 RATHER PERSISTENT BURNING SENSATION & PHOTOPHOBIA ... RECOVERY ... 

 5-10 DAYS. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: 

 Charles C. Thomas Publisher, 1986., p. 144] **PEER REVIEWED** 

 ... STUDIED THE INCIDENCE OF CANCER IN WORKERS IN TWO SEPARATE BERYLLIUM 

 COMPANIES BUT COULD NOT CONCLUDE THAT CANCER AT ANY PARTICULAR SITE COULD 

 BE CORRELATED WITH THE WORKER'S EXPOSURE TO BERYLLIUM. [IARC. Monographs 

 on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: 

 World Health Organization, International Agency for Research on Cancer, 

 1972-PRESENT. (Multivolume work)., p. V1 25 (1972)] **PEER REVIEWED** 

 BECAUSE OF DELAY IN ONSET, CASES OF CHRONIC BERYLLIUM DISEASE FROM OLD 

 EXPOSURES CONTINUE TO DEVELOP. [Hamilton, A., and H. L. Hardy. Industrial 

 Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974., 

 p. 57] **PEER REVIEWED** 

 THE LACK OF SIGNIFICANT ORAL ABSORPTION, ALONG WITH OTHER EVIDENCE 

 INCLUDING THE TOXICITY OF BERYLLIUM, SUGGESTS THAT THE AIRBORNE CONCN ARE 

 MOST HAZARDOUS. [Casarett, L.J., and J. Doull. Toxicology: The Basic 

 Science of Poisons. New York: MacMillan Publishing Co., 1975., p. 462] 

 **PEER REVIEWED** 

 We examined the prevalence of beryllium sensitization in relation to work 

 process and beryllium exposure measurements in a beryllia ceramics plant 

 that had operated since 1980. We interviewed 136 employees (97.8% of the 

 workforce), ascertained beryllium sensitization with the beryllium 

 lymphocyte proliferation blood test, and reviewed historical industrial 

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 hygiene measurements. Of eight beryllium-sensitized employees (5.9%), six 

 (4.4% of participating employees) had granulomatous disease on 

 transbronchial lung biopsy. Machinists had a sensitization rate of 14.3% 

 compared to a rate of 1.2% among other employees. Machining had 

 significantly higher general area and breathing zone measurements than did 

 other processes in the time period in which most beryllium-sensitized 

 cases had started machining work. Daily weighted average estimated of 

 exposure for machining processes also exceeded estimates for other work 

 processes in that time period, with a median daily weighted average of 0.9 

 ug/cu m. Machining process daily weighted averages accounted for the 

 majority of daily weighted averages exceeding the 2.0 ug/cu m OSHA 

 standard, with 8.1% of machining daily weighted averages above the 

 standard. [Kreiss K et al; Am J Industrial Med 30 (1): 16-25 (1996)] 

 **PEER REVIEWED** 

 The first case of chronic beryllium disease at the Rocky Flats 

 Environmental Technology Site (Rocky Flats) was diagnosed in a machinist 

 in 1984. Rocky Flats, located 16 miles northwest of Denver, CO, is part of 

 the US DOE nuclear weapons complex. Research and development operations 

 using beryllium began at Rocky Flats in 1953, and beryllium production 

 operations began in 1957. Exposures could have occurred during foundry 

 operations, casting, shearing, rolling, cutting, welding, machining, 

 sanding, polishing, assembly, and chemical analysis operations. The 

 Beryllium Health Surveillance Program (BHSP) was established in June 1991 

 at Rocky Flats to provide health surveillance for beryllium exposed 

 employees using the Lymphocyte Proliferation Test to identify sensitized 

 individuals. Of the 29 cases of chronic beryllium disease and 76 cases of 

 beryllium sensitization identified since 1991, several cases appear to 

 have had only minimal opportunistic exposures to beryllium, since they 

 were employed in admin functions rather than primary beryllium operations. 

 In conjunction with other health surveillance programs, a questionnaire 

 and interview are admin to obtain detailed work and health histories. 

 These histories, along with other data, are utilized to estimate the 

 extent of an individual's exposure. [Stange AW et al; Toxicol 111 (1-3): 

 213-24 (1996)] **PEER REVIEWED** 

 The occurrence of chronic beryllium disease in a precious metal refinery 

 was investigated. Five workers at a facility that refined and reclaimed 

 gold and silver from industrial scrap developed granulomatous lung disease 

 between 1972 and 1985. The patients were males, four Hispanics and one 

 black, aged 31 to 41 years. The original diagnosis was sarcoidosis. 

 Immunologic studies were performed on the four Hispanic patients utilizing 

 in-vitro proliferative responses of lymphocytes obtained by 

 bronchoalveolar lavage. Hypersensitivity to beryllium salts was found. The 

 entire work force at the facility was surveyed by questionaire and by 

 review of prior X-rays and spirometry results for evidence of 

 granulomatous lung disease. No current workers had radiographic or 

 spirometric evidence suggestive of chronic beryllium disease. Industrial 

 hygiene air monitoring of the facility showed beryllium concentrations of 

 0.22 to 42.3 ug/cu m. Ten percent of the samples were in excess of the 

 current permissible exposure limit of 2.0 ug/cu m. [Cullen MR et al; Am 

 Review Resp Disease 135 (1): 201-8 (1987)] **PEER REVIEWED** 

 The effects of dusts of beryllium metal on the host's local and systemic 

 immune system were reviewed. A primary use for bronchoalveolar lavage in 

 berylliosis was in demonstrating a local immunologic response to 

 beryllium. [Daniels RP; 3rd Int Workshop Immune Responses Induced by 

 Mineral Dusts p.109-119 (1985)] **PEER REVIEWED** 

 The definition of cor pulmonale is heart failure caused by lung disease. 

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 Acute cor pulmonale is associated with disorders that induce severe 

 alveolar hypoxia including pulmonary edema associated with toxic exposures 

 to beryllium. Occupational exposures associated with emboli and 

 obliterative lesions have also been identified as contributing to the 

 disease. Complications of the disease are difficult to treat when the 

 increase in pulmonary vascular resistance is due to blood vessel 

 destruction as in cases of silicosis. The most definitive method for 

 detection, cardiac catheterization, is unsuitable for mass screening. 

 Other methods such as echo cardiography, x-rays, and physical examination 

 are appropriate only late in the progression of the disease. [NIOSH; 

 Occupational Respiratory Diseases (1986) DHHS Pub. NIOSH 86-102] **PEER 

 REVIEWED** 

 Six of 33 breathing zone air samples collected for beryllium analysis 

 showed levels exceeding the NIOSH evaluation criterion of 0.5 

 micrograms/cubic meter. These samples ranged from 7.2 to 0.57 ug/cu m. 

 Thirty three samples collected on beryllium machining equipment were at or 

 below 0.5 ug/cu m. [NIOSH; Health Hazard Evaluation Report No. 

 HETA-84-510-1691, Rockwell International, Rocky Flats Plant, Golden 

 Colorado (1986)] **PEER REVIEWED** 

 This paper describes the beryllium exposure levels and refining processes 

 in a large beryllium factory operating since the 1930s. Lifetime beryllium 

 exposure histories were estimated for the 309 workers present at a health 

 survey conducted in 1977. Beryllium exposure levels in the plant were high 

 for many years, with some estimated exposure levels in excess of 100 ug/cu 

 m. As late as 1975, there were exposures to beryllium above 10 ug/cu m in 

 some jobs. After about 1977, the plant was in compliance with the 

 permissible exposure limit of 2.0 ug/cu m. The median cumulative exposure 

 in this cohort was 65 ug/cu m years and the median duration of exposure 

 was 17 years. From these data a series of exposure parameters, functions 

 of the exposure histories that characterise biologically important 

 dimensions of exposure were calculated for each worker. [Driebel D et al; 

 Br J Ind Med 45 (2): 83-92 (1988)] **PEER REVIEWED** 

 ... We studied 110 subjects divided into three groups of subjects: 

 beryllium disease patients (n=55), beryllium-sensitized patients without 

 disease (n=8), and control subjects (n=47). Evaluation incl completion of 

 a respiratory symptom questionnaire, clinical exam, chest radiograph, 

 spirometry, body plethysmographic lung volumes, and diffusing capacity 

 (DLCO). In the patient groups, we performed max exercise testing with an 

 indwelling arterial line. In addition, we examined BAL and performed blood 

 and BAL beryllium lymphocyte transformation tests (BeLT) as measure of the 

 beryllium-specific T cell-mediated response in these two compartments. In 

 beryllium disease patients we correlated the BAL cellular constituents 

 with clinical parameters indicative of disease severity. Beryllium disease 

 patients exhibited elevated numbers of white cells and lymphocytes in BAL 

 compared with both other groups; however, this lymphocytic alveolitis was 

 significantly obscured in smokers. the BAL cellular constituents 

 correlated with BAL BeLT but not with the blood BeLT. BAL cellular 

 constituents also correlated with the radiographic profusion of small 

 opacities, FEV1/FVC, DLCO, max achievable work load, VO2max, and measures 

 of gas exchange at rest and at max exercise. [Newman LS et al; Am J Resp 

 Critical Care Med 150 (1): 135-142 (1994)] **PEER REVIEWED** 

 In this letter to the editor and a reply, earlier reports of an excess of 

 lung cancer occurring among patients with beryllium disease were 

 considered. Of the 689 patients in the study, 28 died of lung cancer that 

 developed after entry into the registry. Of the 689 patients, 235 were 

 suffering from acute beryllium disease and 17 of these died of lung 

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 cancer. All 17 of these patients had a history of employment at a facility 

 in Lorain, OH, where the exposure levels were high. The Lorain facility 

 had employed 61% of all patients who had acute beryllium disease reported 

 to the registry. There may have been a confounding factor in the Lorain 

 cohort which may have been cigarette smoking of another carcinogen. 

 Exposure to workers has been reduced more than 100 fold below those that 

 existed when the Lorain facility was in operation. In the response, the 

 authors of the original study indicated that the sparse numbers make it 

 difficult to draw any conclusions about lung cancer risk at Lorain versus 

 the other facilities. [Eisenbud M et al; J Nat Can Inst 85 (20): 1697-1699 

 (1993)] **PEER REVIEWED** 

 ... Of 18 new cases of beryllium sensitization, 12 had beryllium disease, 

 and three more developed pulmonary granulomas on lung biopsy over the 

 succeeding 2 yr. Beryllium-sensitized cases did not differ from noncases 

 in age, gender, race, ethnicity, smoking, most respiratory symptoms, 

 spirometric or radiographic abnormalities, or job tenure. The six 

 sensitized cases without initial disease differed from beryllium disease 

 cases in having greater pack-years of smoking. Sensitization occurred 

 among workers with inadvertent or bystander exposure, such as a secretary 

 and security guard. However, beryllium sensitization risk was higher for 

 machinists (4.7%) and for persons reporting measured overexposure (7.4%, 

 odds ratio 5.1); exposure beginning before 1970 (3.6%, odds ratio 2.7); 

 consistent beryllium exposure (3.4%); and sawing (4.7%) or band sawing 

 (6.0%) of beryllium metal. [Kreiss K et al; Am Rev Respir Dis 148 (4-1): 

 985-91 (1993)] **PEER REVIEWED** 

 Nine new cases of biopsy-confirmed chronic beryllium disease were 

 identified among 505 employees and ex-employees in a company that had 

 manufactured beryllia ceramics from 1958 to 1975. Of tests commonly used 

 in medical surveillance, only a confirmed blood beryllium lymphocyte 

 transformation test had a high positive predictive value for beryllium 

 disease (100%). However, two beryllium disease cases had either a normal 

 or inconsistently abnormal blood test and were identified for diagnostic 

 work-up by abnormal chest radiography. The only risk factor for beryllium 

 disease was beryllium exposure. Degree of exposure was assoc with disease 

 rates, which ranged from 2.9% to 15.8% for beryllia-exposed subgroups. 

 [Kreiss K et al; J Occup Med 35 (3): 267-274 (1993)] **PEER REVIEWED** 

 STUDY WAS UNDERTAKEN OF MORTALITY PATTERNS AMONG WHITE MALES ENTERED INTO 

 BERYLLIUM CASE REGISTRY (BCR) WHILE ALIVE WITH A DIAGNOSIS OF BERYLLIUM 

 RELATED NONNEOPLASTIC RESPIRATORY SYMPTOMS OR DISEASE. ANALYSES 

 DEMONSTRATE AN EXCESSIVE RISK OF LUNG CANCER AMONG THOSE SUBJECTS IN THE 

 BERYLLIUM CASE REGISTRY WHO HAD BEEN PREVIOUSLY DIAGNOSED WITH ACUTE 

 CHEMICAL PNEUMONITIS OR BRONCHITIS SECONDARY TO SHORT-TERM BERYLLIUM 

 EXPOSURE. IN THE EVALUATION OF THE EXCESSIVE LUNG CANCER RISK IN THIS 

 POPULATION, CONSIDERATION SHOULD BE GIVEN TO THE COMPETING EFFECTS FROM 

 THE HIGH CASE FATALITY RATE OF NONNEOPLASTIC RESPIRATORY DISEASE. THIS 

 EXCESSIVE RISK OF LUNG CANCER COULD NOT BE EXPLAINED ON THE BASIS OF 

 CIGARETTE SMOKING PER SE. THE FINDINGS OF THE PRESENT STUDY UTILIZING 

 SUBJECTS IN THE BERYLLIUM CASE REGISTRY ARE CONSISTENT WITH RESULTS OF 

 ANIMAL STUDIES THAT OVER 30 YR AGO FIRST DEMONSTRATED BERYLLIUM TO BE A 

 CARCINOGEN & WITH NUMEROUS EPIDEMIOLOGIC STUDIES DEMONSTRATING AN 

 INCREASED RISK OF LUNG CANCER AMONG WORKERS OCCUPATIONALLY EXPOSED TO 

 BERYLLIUM & ITS COMPOUNDS. /BERYLLIUM & BERYLLIUM CMPD/ [INFANTE 

 PF ET AL; ENVIRON RES 21 (1): 35-43 (1980)] **PEER REVIEWED** 

 Chronic beryllium disease is the pulmonary and systemic granulomatous 

 disease caused by exposure to beryllium by inhalation. In most cases, the 

 duration of exposure is several months to years. The interval between 

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 initial exposure and the clinical manifestations of disease varies. Some 

 patients become symptomatic while actively working; others, as late as 25 

 years after their last exposure. The average latency period is 10 to 15 

 years. Exertional dyspnea is the most common symptom of chronic beryllium 

 disease. Other symptoms are cough, fatigue, weight loss, chest pain, and 

 arthralgias. Physical findings may be entirely normal or may include 

 bibasilar crackles, lymphadenopathy, skin lesions, hepatosplenomegaly, and 

 clubbing. Signs of pulmonary hypertension may be present in severe, 

 long-standing disease. Parotid gland enlargement was reported in one 

 patient with chronic beryllium disease. /Beryllium and compounds/ [Rom, 

 W.N. (ed.). Environmental and Occupational Medicine. 2nd ed. Boston, MA: 

 Little, Brown and Company, 1992., p. 782] **PEER REVIEWED** 

 Nodular skin lesions have been described in patients with chronic 

 beryllium disease whose beryllium exposure was by inhalation only, not be 

 direct skin contact. Biopsies in these cases have shown noncaseating 

 granulomas. Beryllium also causes contact dermatitis by both direct 

 irritation and sensitization. The use of patch testing has been curtailed 

 because of reports of exacerbations of respiratory disease related to this 

 test. Conjunctivitis, periorbital edema, and upper respiratory tract 

 involvement may accompany dermatitis. Beryllium ulcers caused by 

 implantation of a soluble beryllium compound in a skin abrasion and 

 requiring curettage of the ulcer base for treatment have also been 

 reported. /Beryllium and compounds/ [Rom, W.N. (ed.). Environmental and 

 Occupational Medicine. 2nd ed. Boston, MA: Little, Brown and Company, 

 1992., p. 787] **PEER REVIEWED** 

 Acting as a direct irritant, beryllium may cause acute nasopharyngitis, 

 tracheobronchitis, or chemical pneumonitis. The severity of the clinical 

 disease depends largely on the dose of beryllium exposure. Chemical 

 pneumonitis may be severe after a brief exposure to high concentrations of 

 beryllium or subacute in onset and course after prolonged exposure to 

 lower concentrations. Symptoms and signs are nonspecific, identical to 

 those found in any case of chemical pneumonitis secondary to a lung 

 irritant, and include dyspnea, cough, chest pain, blood-tinged sputum, 

 tachycardia, crackles, and in severe cases cyanosis. Radiographs show 

 diffuse or localized infiltrates, and pulmonary function tests show 

 reduced lung volumes and hypoxemia. /Beryllium and compounds/ [Rom, W.N. 

 (ed.). Environmental and Occupational Medicine. 2nd ed. Boston, MA: 

 Little, Brown and Company, 1992., p. 786] **PEER REVIEWED** 

 A case-control study on parental occupation and childhood cancer carried 

 out in Denver, CO, USA, included 252 cases of childhood cancer diagnosed 

 during 1976-83 and 222 population controls selected by random-digit 

 dialing. A job-exposure matrix was used to assign parental exposures for 

 six months or longer during the year prior to the child's birth on the 

 basis of job titles. Odds ratios were estimated for all cancers, acute 

 lymphocytic leukemia and brain cancer, after adjusting for age at 

 diagnosis, year of diagnosis, sex, mother's age at time of birth, maternal 

 smoking during pregnancy, birth weight, birth order and indicators of 

 social class. When all cancers were considered, no association was found 

 between childhood cancer and exposure to beryllium or its compounds for 

 either the mother or the father (odds ratio, 1.0; 95% CI, 0.1-7.1; based 

 on two exposed cases; and 1.6;0.6-4.4; based on 17 exposed cases, 

 respectively). When the exposures of the fathers were analyzed for 

 specific types of cancer, an elevated odds ratio was found for brain 

 cancer (2.1; 0.6-7.6; 5 cases) but not for acute lymphocytic leukemia 

 (1.3; 0.3-5.9; 5 cases). Most of the subjects considered to have been 

 exposed to beryllium were electrical equipment assemblers and installers 

 (67%), metal processes and welders (20%). /Beryllium and beryllium 

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 compounds/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of 

 Chemicals to Man. Geneva: World Health Organization, International Agency 

 for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V58 75 

 (1993)] **PEER REVIEWED** 

 Exposure to beryllium compounds may cause an acute chemical pneumonitis, 

 tracheobronchitis, conjunctivitis, dermatitis and chronic granulomatous 

 pulmonary disease with systemic manifestations. The acute pulmonary 

 disease was first described in Germany in 1933 and the chronic form in the 

 USA in 1946. /Beryllium and beryllium compounds/ [IARC. Monographs on the 

 Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World 

 Health Organization, International Agency for Research on Cancer, 

 1972-PRESENT. (Multivolume work)., p. V58 88 (1993)] **PEER REVIEWED** 

 Acute beryllium disease, most frequently related to intense but brief 

 exposure, consists of respiratory tract irritation and dermatitis, 

 sometimes with conjunctivitis. The respiratory tract symptoms range from 

 mild nasopharyngitis to a severe chemical pulmonitis, which may be fatal. 

 In fatal cases, histopathological findings in the lungs have included 

 interstitial oedema, cellular infiltration, elevated numbers of plasma 

 cells, alveolar cell proliferation or desquamation and, sometimes, 

 interalveolar oedema, hyaline membranes and organizing pneumonia. 

 /Beryllium and beryllium compounds/ [IARC. Monographs on the Evaluation of 

 the Carcinogenic Risk of Chemicals to Man. Geneva: World Health 

 Organization, International Agency for Research on Cancer, 1972-PRESENT. 

 (Multivolume work)., p. V58 88 (1993)] **PEER REVIEWED** 

 Chronic beryllium disease is a systemic disorder with primary 

 manifestations in the lung, characterized by a decrease in transfer factor 

 with restrictive and obstructive ventilatory function. 

 Histopathologically, the disease is characterized by non-caseating 

 granuloma formation with giant cells, as in sarcoidosis, primarily seen in 

 the lungs but also in other tissues. Chest radiography usually shows 

 diffuse infiltrates and hilar adenopathy. An improvement in lung function 

 and even in lung radiographic findings was reported after a significant 

 decrease in the air concentration of beryllium due to improved engineering 

 and ventilation in plants. /Beryllium and beryllium compounds/ [IARC. 

 Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. 

 Geneva: World Health Organization, International Agency for Research on 

 Cancer, 1972-PRESENT. (Multivolume work)., p. V58 88 (1993)] **PEER 

 REVIEWED** 

 Although chronic beryllium disease has become rare since the adoption of 

 stringent industrial hygiene measures, sporadic cases are sill reported, 

 e.g., among workers in a precious metal refinery, where exposure to 

 beryllium did not exceed 2 ug/cu m. A conspicuous feature of chronic 

 beryllium disease is its occasional occurrence outside facilities in which 

 beryllium compounds are used: 10 cases /were reported/ among people who 

 had never worked in a beryllium plant but who lived within 1 km of one; 

 the best estimate of beryllium concentrations in the air in the area was 

 0.01-0.1 ug/cu m. In 1983, when the US registry for beryllium diseases 

 contained 622 cases of chronic beryllium disease, 65 had had no 

 occupational exposure to beryllium, 42 could be attributed to air 

 pollution (41 occurred in the vicinity of tow large production plants and 

 one in a woman living near a fluorescent-lamp plant) and 23 two household 

 exposure to dust brought home on work clothes. /Beryllium and beryllium 

 compounds/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of 

 Chemicals to Man. Geneva: World Health Organization, International Agency 

 for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V58 88 

 (1993)] **PEER REVIEWED** 

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 In a cohort study of 9225 male workers employed in seven beryllium 

 processing facilities in the USA, the SMR for pneumoconiosis and other 

 respiratory diseases was 1.48 (95% CI, 1.21-1.80), that for diseases of 

 the heart was 1.06 (1.00-1.12) and that for chronic and unspecified 

 nephritis, renal failure and other renal sclerosis. /Beryllium and 

 beryllium compounds/ [IARC. Monographs on the Evaluation of the 

 Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, 

 International Agency for Research on Cancer, 1972-PRESENT. (Multivolume 

 work)., p. V58 89 (1993)] **PEER REVIEWED** 

 A nonsymptomatic form of chronic beryllium disease - typical granulomatous 

 changes in transbronchial biopsy specimens with positive lymphocyte 

 transformation tests - has been reported. /Beryllium and beryllium 

 compounds/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of 

 Chemicals to Man. Geneva: World Health Organization, International Agency 

 for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V58 89 

 (1993)] **PEER REVIEWED** 

 Beryllium dermatitis may be typical contact dermatitis, localized dermal 

 ulceration or a subcutaneous granuloma. Ulceration of granulomas develops 

 after a particle of a beryllium-containing substance is introduced into an 

 abrasion, laceration or cut. People with beryllium-induced contact 

 dermatitis react to patch testing. Patch testing may cause a flare of the 

 dermatitis in sensitized people; it may also induce beryllium sensitivity. 

 /Beryllium and beryllium compounds/ [IARC. Monographs on the Evaluation of 

 the Carcinogenic Risk of Chemicals to Man. Geneva: World Health 

 Organization, International Agency for Research on Cancer, 1972-PRESENT. 

 (Multivolume work)., p. V58 89 (1993)] **PEER REVIEWED** 

 The pregnancy of a 25 year old women who worked in a fluorescent-tube 

 factory in 1942-44 /was described/. She displayed signs of radiographic 

 changes in lungs, cyanosis and dyspnoea in the seventh month of her second 

 pregnancy in 1950. No beryllium was detected in a lung biopsy. The woman 

 was treated with adrenocorticotrophic hormone and steroids and delivered a 

 2.75 kg child seven weeks later. Twenty-four hour specimens of the urine 

 of the infant collected on the second and third day after birth contained 

 0.4 and 0.015 ug Be. The child became severely hypoglycemic after 48 hours 

 but was subsequently released from the hospital. /Beryllium and beryllium 

 compounds/ [IARC. Monographs on the Evaluation of the Carcinogenic Risk of 

 Chemicals to Man. Geneva: World Health Organization, International Agency 

 for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V58 92 

 (1993)] **PEER REVIEWED** 

 A subset of people covered by the 1980 US National Natality and Fetal 

 Mortality Surveys for indications of adverse effects related to maternal 

 or paternal occupational exposures to beryllium, as assessed from a 

 job-exposure matrix. Paternal occupational exposure was associated with 

 3170 stillbirths, 552 preterm deliveries and 371 babies small for 

 gestational age; the corresponding odds ratios (with 95% CI) were: 1.0 

 (0.7-1.3), 1.0 (0.5-2.0) and 0.9 (0.5-1.7), respectively. Maternal 

 exposure to beryllium was not associated with these end-points. /Beryllium 

 and beryllium compounds/ [IARC. Monographs on the Evaluation of the 

 Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, 

 International Agency for Research on Cancer, 1972-PRESENT. (Multivolume 

 work)., p. V58 92 (1993)] **PEER REVIEWED** 

MEDICAL SURVEILLANCE: 

 IN A STUDY OF OCCUPATIONAL LIVER DISEASES, IT WAS NOTED THAT BERYLLIUM 

 WORKERS FREQUENTLY EXPERIENCE GRANULOMATOUS HEPATITIS WHICH CAN BE 

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 CONFIRMED BY A POSITIVE PATCH TEST WITH BERYLLIUM FLUORIDE OR SULFATE, OR 

 CONFIRMING THE PRESENCE OF BERYLLIUM IN THE TISSUES OR URINE. 

 [POWELL-JACKSON P, DAVIS M; PRACTITIONER 223 (1333): 67 (1979)] **PEER 

 REVIEWED** 

 Laser ion mass analysis (LIMA) was tested as a method for diagnosing 

 chronic beryllium disease (CBD). Fourteen patients satisfied the 

 diagnostic criteria for chronic beryllium disease. Five patients were 

 included who had incomplete evidence of chronic beryllium disease and 13 

 control subjects were also examined. Beryllium was detected in 13 of the 

 14 definite cases. The negative result with a positive bulk analysis was 

 surprising, and a repeat test gave a positive result. The beryllium 

 lymphocyte transformation test (BeLT) test was positive in 8 of 10 tested, 

 and all eight were laser ion mass analysis positive. Both beryllium 

 lymphocyte transformation test negative cases were laser ion mass analysis 

 positive. In the suspect group only one case was laser ion mass analysis 

 positive. The beryllium lymphocyte transformation test was negative in all 

 four patients tested. Of the 13 control patients, beryllium was absent in 

 the two with normal lungs, one with tuberculotic lung, and seven with 

 sarcoidosis lungs. Both samples of coal workers pneumoconiosis were laser 

 ion mass analysis positive. [Williams WJ, Kelland D; J Clin Pathol 39 (8): 

 900-1 (1986)] **PEER REVIEWED** 

 A study was performed to assess the value of the lymphocyte transformation 

 test (LTT) as a diagnostic tool in the surveillance of individuals exposed 

 to beryllium /for/ 20 years. Analysis of venous blood showed that three 

 beryllium exposed workers had a positive lymphocyte transformation test 

 following stimulation for 4 days with three or five different beryllium 

 concentrations. After 6 days, similar results were obtained. Two of the 

 workers with positive lymphocyte transformation test had a diagnosis of 

 diffuse granulomatous lung disease consistent with chronic berylliosis. 

 Lymphocyte transformation test can be a valuable aid in the differential 

 diagnosis of granulomatous lung diseases in beryllium exposed individuals, 

 especially since the other differential diagnostic criteria are all based 

 on nonspecific clinical and epidemiological measurements. The lymphocyte 

 transformation test should therefore be included in the medical 

 surveillance program of beryllium workers. [Bargon J et al; Eur J Resp 

 Diseases 669 (146): 211-5 (1986)] **PEER REVIEWED** 

 ... Since inhalation of this element can induce chronic beryllium disease 

 ... an antibody assay was developed to screen workers for internal 

 exposure to beryllium. Exposure is indicated by a titer of antibodies 

 greater than two standard deviations above a normal population control. 

 ... [Clarke SM et al; Toxicol Industrial Health 11 (4): 399-411 (1995)] 

 **PEER REVIEWED** 

 PRECAUTIONS FOR "CARCINOGENS": ... In relation specifically to cancer 

 hazards, there are at present no health monitoring methods that may ensure 

 the early detection of preneoplastic lesions or lesions which may preclude 

 them. Whenever medical surveillance is indicated, in particular when 

 exposure to a carcinogen has occurred, ad hoc decisions should be taken 

 concerning additional tests that might become useful or mandatory. 

 /Chemical Carcinogens/ [Montesano, R., H. Bartsch, E.Boyland, G. Della 

 Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis 

 (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of 

 Safety. IARC Scientific Publications No. 33. Lyon, France: International 

 Agency for Research on Cancer, 1979., p. 23] **PEER REVIEWED** 

 At present, laboratory tests are not available to determine susceptibility 

 to beryllium sensitization and the potential to develop chronic beryllium 

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 disease. Individuals with pulmonary impairment in the moderate or severe 

 category of either volume, flow, or diffusion should be carefully 

 evaluated before assignment to areas of high potential risk of exposure. 

 Both preplacement and annual surveillance examinations should include 1. A 

 detailed medical and pulmonary history. 2. A 14" X 17" PA chest 

 radiograph. 3. Pulmonary function measurements, including FVC and FEV. 4. 

 Additional pulmonary function parameters such as carbon monoxide diffusion 

 capacity. Greater frequency of these measurements increases the 

 sensitivity of the parameter and improves early identification of subtle 

 changes. /Beryllium and compounds/ [Zenz, C., O.B. Dickerson, E.P. 

 Horvath. Occupational Medicine. 3rd ed. St. Louis, MO., 1994, p. 479] 

 **PEER REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 NIOSH (NOES Survey 1981-1983) has statistically estimated that 14,000 

 workers (740 of these are female) are potentially exposed to beryllium in 

 the USA(1). Occupational exposure to beryllium may be through inhalation 

 of airborne dust and dermal contact with beryllium at workplaces where it 

 is produced or used(SRC). Limited monitoring data indicate that the 

 general population will be exposed to beryllium via inhalation of ambient 

 air, and ingestion of contaminated food and drinking water. The most 

 probable human exposure would be occupational exposure(SRC). [(1) NIOSH; 

 National Occupational Exposure Survey (NOES) (1983)] **PEER REVIEWED** 

 The influence of aerosol suspension from clothing on personal monitor 

 exposure estimates was investigated in a beryllium facility. Samples of 

 100% cotton and 100% Nomex fabrics used at the beryllium facility were 

 tested. The deposition of airborne beryllium into fabrics was 

 significantly enchanced by electrostatic attraction on cotton but not on 

 Nomex fabrics. Both fabrics collected more beryllium in motion than on 

 stationary units. Personal monitors mounted in front of fabrics collected 

 more beryllium when the fabrics were agitated than when monitors were 

 placed in the positions of the nose and mouth. The air concentrations 

 increased as fabric load increased, but leveled off at high fabric load 

 concentrations. Resuspension from cotton was higher than from Nomex. 

 Resuspension of aerosol from garments can cause erroneously high exposure 

 measurements from chest mounted personal monitors. [Bohne JE, Cohen BS; Am 

 Ind Hyg Assoc J 46 (2): 73-9 (1985)] **PEER REVIEWED** 

 Workshirts worn by employees at a beryllium refinery resuspended beryllium 

 containing dust. The old shirts resuspended significantly higher 

 quantities of beryllium to the air than did the washed and unwashed new 

 shirts. A considerable fraction of the Be measured in air was respirable. 

 [Cohen BS, Positano R; Am Ind Hyg Assoc J 47 (5): 255-8 (1986)] **PEER 

 REVIEWED** 

 Fourteen dental casting alloys were analyzed for release of nickel and 

 beryllium into acidic salivary soln in vitro. Corrosion rates at varying 

 pH levels and time in soln were calc over a 120 day period and the 

 possible significance of these rates to allergic reactions or other health 

 hazards were postulated. When the beryllium levels were analyzed for these 

 alloys they were much higher than expected. In each of the alloys, since 

 the nickel cmpd was often 66-78% of the cmpd and the beryllium level a max 

 of 2%, the differences in magnitude of nickel vs beryllium concn might be 

 expected to be on the order of 30/1 or greater. The differences were 

 closer to 8/1. Nickel and beryllium containing dental casting alloys have 

 the potential to be a significant hazard to the lab technician, dentist 

 and patient. [Covington JS et al; J Prosthet Dent 54 (1): 127-36 (1985)] 

 **PEER REVIEWED** 

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 OSHA estimates that approx 25,000 workers are exposed to beryllium. Among 

 these are beryllium ore miners, beryllium alloy makers and fabricators, 

 phosphorus manufacturers, ceramic workers, missile technicians, nuclear 

 reactor workers, electric and electronic equipment workers and jewelers. 

 /Beryllium/ [Sittig, M. Handbook of Toxic and Hazardous Chemicals and 

 Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 

 1985., p. 126] **PEER REVIEWED** 

BODY BURDEN: 

 STORAGE OF BERYLLIUM IN ALL MAJOR TISSUE SITES IS OF LONG DURATION, 

 PARTICULARLY IN THE PULMONARY LYMPH NODES & BONE. HENCE ELIMINATION OF 

 BERYLLIUM FROM THE BODY IS EXTREMELY SLOW, & THE LAST 5% REQUIRING 

 MANY MONTHS OR YEARS TO DISAPPEAR COMPLETELY FROM THESE LATTER TWO SITES. 

 [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and 

 Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley 

 Sons, 1981-1982., p. 1546] **PEER REVIEWED** 

TOXICITY SUMMARY: 

 Exposure of people to relatively high concentrations of beryllium (greater 

 than 100 ug cu m) causes acute beryllium disease, characterized by 

 chemical pneumonitis. ... Some people inhaling low concentrations of 

 beryllium develop chronic beryllium disease, a granulomatous lung disease 

 characterized by dyspnea, cough, reduced pulmonary function, and a variety 

 of other symptoms, including weight loss. ... The lack of a dose-response 

 relationship between the extent of exposure and development of the 

 disease, long latency period between exposure and onset, and the low 

 incidence among beryllium-exposed individuals suggests that the disease is 

 immune mediated. ... Occupational risk associated with exposure to 

 beryllium-containing alloys has been documented for individuals exposed to 

 beryllium-copper and beryllium-nickel alloys. Beryllium is a suspected 

 human carcinogen, based on results of animal data. Epidemiologic evidence 

 relating beryllium exposure to cancer in humans is inadequate to 

 demonstrate or refute that beryllium is carcinogenic in humans, and the 

 International Agency for Research on Cancer lists the evidence for 

 beryllium induced carcinogenicity in humans as "limited". ... The 

 pulmonary effects of inhaled beryllium have also been evaluated in a 

 variety of laboratory animal species. ... monkeys exposed to relatively 

 high concentrations of beryllium compounds developed symptoms and 

 histopathological findings consistent with acute beryllium disease. ... 

 Granulomatous lung disease has also been produced in guinea pigs exposed 

 to beryllium compounds by inhalation or by intratracheal instillation. ... 

 Repeated inhalation of beryllium-containing materials, including soluble 

 beryllium compounds by various strains of laboratory rats has resulted in 

 development of inflammatory and proliferative changes, granulomatous lung 

 changes, and the development of lung tumors. Although beryllium- exposed 

 rats have developed various degrees of granulomatous lung disease, none 

 have developed immunopathological responses in lung or beryllium 

 hypersensitivity. ... studies have shown that several strains of mice 

 inhaling beryllium develop pulmonary lesions with features consistent with 

 chronic beryllium disease. Lung lesions consisted of infiltration of 

 lymphocytes into the lung interstitium, development of microgranulomas 

 consisting of T lymphocytes and macrophages, and the presence of some 

 pulmonary fibrosis. Under certain exposure conditions, increased numbers 

 of lymphocytes were recovered in bronchoalveolar lavage fluid from exposed 

 animals. [Chang, L.W. (ed.). Toxicology of Metals. Boca Raton, FL: Lewis 

 Publishers, 1996, p. 929-30] **PEER REVIEWED** 

EVIDENCE FOR CARCINOGENICITY: 

 WEIGHT OF EVIDENCE CHARACTERIZATION: B1; probable human carcinogen. Based 

 on the limited evidence of carcinogenicity in humans exposed to airborne 

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 beryllium (lung cancer) and sufficient evidence of carcinogenicity in 

 animals (lung cancer in rats and monkeys inhaling beryllium, lung tumors 

 in rats exposed to beryllium via intratracheal instillation, and 

 osteosarcomas in rabbits and possibly mice receiving intravenous or 

 intramedullary injection), beryllium is reclassified from a B2 (inadequate 

 human data) to a B1 probable human carcinogen (limited human data) using 

 criteria of the 1986 Guidelines for Carcinogen Risk Assessment. Using the 

 proposed Guidelines for Carcinogen Risk Assessment, inhaled beryllium 

 would be characterized as a "likely" carcinogen in humans, and the human 

 carcinogenic potential of ingested beryllium cannot be determined. Studies 

 regarding the potential carcinogenicity of ingested beryllium to humans 

 were not available. Increases in lung cancer mortality have been observed 

 in cohort mortality studies of beryllium processing workers ... and in 

 studies of entrants on the BCR. No increases in other types of cancer were 

 found, but increases in deaths from nonmalignant respiratory disease were 

 also observed. Newer studies ... have been considered as the basis for a 

 dose-response assessment, but share a limitatiion ... lack of individul 

 exposure monitoring or job history data that would support a more 

 definitive exposure assessment. NIOSH has recently completed a lung cancer 

 case-control study nested within a cohort mortality study of beryllium 

 manufacturing workers at the Reading beryllium processing facility. The 

 study developed an exposure matrix and calculated airborne exposure 

 concentration and thus may provide the best available basis for a 

 quantitative cancer estimate. ... Chronic oral studies of the potential 

 carcinogenicity of beryllium in animals were conducted at dose levels 

 below the /Maximum Tolerated Dose/, and therefore are inadequate for the 

 assessment of carcinogenicity. Beryllium has been shown to induce lung 

 cancer in rats exposed to beryllium by both inhalation and intratracheal 

 instillation and in monkeys by inhalation. Osteosarcomas have been 

 produced in rabbits and possibly in mice by intravenous and intramedullary 

 injection using a variety of beryllium compounds and beryllium metal. No 

 tumors were produced by intracutaneous or percutaneous injections of 

 beryllium compounds. The majority of studies do not induce gene mutation 

 in bacterial assays with or without metabolic activation. Gene mutations 

 have been observed in mammalian cells cultured with beryllium chloride. 

 Culturing mammalian cells with beryllium chloride, beryllium sulfate, or 

 beryllium nitrate has resulted in clastogenic alterations. HUMAN 

 CARCINOGENICITY DATA: Limited. ANIMAL CARCINOGENICITY DATA: Sufficient. 

 [U.S. Environmental Protection Agency's Integrated Risk Information System 

 (IRIS) for Beryllium and compounds (7440-41-7) Available from: 

 http://www.epa.gov/ngispgm3/iris on the Substance File List as of March 

 15, 2000] **QC REVIEWED** 

 Evaluation: There is sufficient evidence in humans for the carcinogenicity 

 of beryllium and beryllium compounds. There is sufficient evidence in 

 experimental animals for the carcinogenicity of beryllium and beryllium 

 compounds. Overall evaluation: Beryllium and beryllium compounds are 

 carcinogenic to humans (Group 1). /Beryllium and beryllium compounds/ 

 [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals 

 to Man. Geneva: World Health Organization, International Agency for 

 Research on Cancer, 1972-PRESENT. (Multivolume work)., p. 58 103 (1993)] 

 **PEER REVIEWED** 

 A1: Confirmed human carcinogen. /Beryllium and compounds, as Be/ [American 

 Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold 

 Limit Values for Chemical Substances and Physical Agents and Biological 

 Exposure Indices. Cincinnati, OH, 2008, p. 14] **QC REVIEWED** 

 Beryllium and Beryllium Compounds: known to be human carcinogens. 

 [DHHS/National Toxicology Program; Eleventh Report on Carcinogens: 

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 Beryllium and Beryllium Compounds (January 2005). Available from, as of 

 July 31, 2009: 

 http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s022bery.pdf ] **QC 

 REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 NIOSH (NOES Survey 1981-1983) has statistically estimated that 14,000 

 workers (740 of these are female) are potentially exposed to beryllium in 

 the USA(1). Occupational exposure to beryllium may be through inhalation 

 of airborne dust and dermal contact with beryllium at workplaces where it 

 is produced or used(SRC). Limited monitoring data indicate that the 

 general population will be exposed to beryllium via inhalation of ambient 

 air, and ingestion of contaminated food and drinking water. The most 

 probable human exposure would be occupational exposure(SRC). [(1) NIOSH; 

 National Occupational Exposure Survey (NOES) (1983)] **PEER REVIEWED** 

 The influence of aerosol suspension from clothing on personal monitor 

 exposure estimates was investigated in a beryllium facility. Samples of 

 100% cotton and 100% Nomex fabrics used at the beryllium facility were 

 tested. The deposition of airborne beryllium into fabrics was 

 significantly enchanced by electrostatic attraction on cotton but not on 

 Nomex fabrics. Both fabrics collected more beryllium in motion than on 

 stationary units. Personal monitors mounted in front of fabrics collected 

 more beryllium when the fabrics were agitated than when monitors were 

 placed in the positions of the nose and mouth. The air concentrations 

 increased as fabric load increased, but leveled off at high fabric load 

 concentrations. Resuspension from cotton was higher than from Nomex. 

 Resuspension of aerosol from garments can cause erroneously high exposure 

 measurements from chest mounted personal monitors. [Bohne JE, Cohen BS; Am 

 Ind Hyg Assoc J 46 (2): 73-9 (1985)] **PEER REVIEWED** 

 Workshirts worn by employees at a beryllium refinery resuspended beryllium 

 containing dust. The old shirts resuspended significantly higher 

 quantities of beryllium to the air than did the washed and unwashed new 

 shirts. A considerable fraction of the Be measured in air was respirable. 

 [Cohen BS, Positano R; Am Ind Hyg Assoc J 47 (5): 255-8 (1986)] **PEER 

 REVIEWED** 

 Fourteen dental casting alloys were analyzed for release of nickel and 

 beryllium into acidic salivary soln in vitro. Corrosion rates at varying 

 pH levels and time in soln were calc over a 120 day period and the 

 possible significance of these rates to allergic reactions or other health 

 hazards were postulated. When the beryllium levels were analyzed for these 

 alloys they were much higher than expected. In each of the alloys, since 

 the nickel cmpd was often 66-78% of the cmpd and the beryllium level a max 

 of 2%, the differences in magnitude of nickel vs beryllium concn might be 

 expected to be on the order of 30/1 or greater. The differences were 

 closer to 8/1. Nickel and beryllium containing dental casting alloys have 

 the potential to be a significant hazard to the lab technician, dentist 

 and patient. [Covington JS et al; J Prosthet Dent 54 (1): 127-36 (1985)] 

 **PEER REVIEWED** 

 OSHA estimates that approx 25,000 workers are exposed to beryllium. Among 

 these are beryllium ore miners, beryllium alloy makers and fabricators, 

 phosphorus manufacturers, ceramic workers, missile technicians, nuclear 

 reactor workers, electric and electronic equipment workers and jewelers. 

 /Beryllium/ [Sittig, M. Handbook of Toxic and Hazardous Chemicals and 

 Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 

 1985., p. 126] **PEER REVIEWED** 

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BODY BURDEN: 

 STORAGE OF BERYLLIUM IN ALL MAJOR TISSUE SITES IS OF LONG DURATION, 

 PARTICULARLY IN THE PULMONARY LYMPH NODES & BONE. HENCE ELIMINATION OF 

 BERYLLIUM FROM THE BODY IS EXTREMELY SLOW, & THE LAST 5% REQUIRING 

 MANY MONTHS OR YEARS TO DISAPPEAR COMPLETELY FROM THESE LATTER TWO SITES. 

 [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and 

 Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley 

 Sons, 1981-1982., p. 1546] **PEER REVIEWED** 

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The following information was generated from the 

Hazardous Substances Data Bank (HSDB), 

a database of the National Library of Medicine's TOXNET system 

(http://toxnet.nlm.nih.gov) on October 27, 2009. 

Query: The chemical name boron was identified. 

The following terms were added from ChemIDplus: 

CAS Registry Number: 7440-42-8 

1 

NAME: BORON, ELEMENTAL 

RN: 7440-42-8 

NOTE: 

 This record contains information for boron in its zero valence state only. 

 For general toxicity and environmental fate of boron ions and boron 

 compounds, refer to the BORON COMPOUNDS record; for compound specific 

 information, refer to the appropriate individual records, e.g., 

 triethylboron, pentaborane, etc. 

HUMAN HEALTH EFFECTS: 

TOXICITY SUMMARY: 

 IDENTIFICATION: (Elemental boron exists as a solid at room temperature, 

 either as black monoclinic crystals or as a yellow or brown amorphous 

 powder when impure). It is a naturally occurring element that is found in 

 the form of borates in the oceans, sedimentary rocks, coal, shale, and 

 some soils. Boron enters the environment mainly through the weathering of 

 rocks, boric acid volatilization from seawater, and volcanic activity. 

 Boron is also released from anthropogenic sources to a lesser extent. 

 These sources include agricultural, refuse, and fuel wood burning, power 

 generation using coal and oil, glass product manufacture, use of 

 borates/perborates in the home and industry, borate mining/processing, 

 leaching of treated wood/paper, and sewage/sludge disposal. HUMAN 

 EXPOSURE: Only a few human studies have been conducted to assess health 

 effects associated with exposure to boron compounds. The available data 

 show that exposure is associated with short-term irritant effects on the 

 upper respiratory tract, nasopharynx, and eye. These effects, however, 

 appear to be short-term and reversible. The sole long-term (7-year) 

 follow-up study failed to identify any long-term health effects. No 

 studies have been identified that assess reproductive outcomes. Based on 

 the lack of human data and the limited animal data, boron is not 

 classifiable as to its human carcinogenicity. ANIMAL STUDIES: Data 

 regarding developmental and reproductive toxicity show that lower fetal 

 body weight in rats is the critical effect. As dose level increases, the 

 effects seen include: further rib effects and testicular pathology in the 

 rat, decreased fetal body weight and increased fetal cardiovascular 

 malformations in the rabbit, and severe testicular pathology in the rat; 

 testicular atrophy and sterility in the rat; reduced fetal body weight in 

 the mouse. Animal studies on mice and rats showed no evidence of 

 carcinogenicity of boric acid. /Boron and Boron compounds/ [World Health 

 Organization/International Programme on Chemical Safety. Environmental 

 Health Criteria 204. Boron pp. 1-10 (1998)] **PEER REVIEWED** 

HUMAN TOXICITY EXCERPTS: 

 /OTHER TOXICITY INFORMATION/ Elemental boron is not considered to be a 

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 poison ... [Weast, R.C. (ed.) Handbook of Chemistry and Physics. 69th ed. 

 Boca Raton, FL: CRC Press Inc., 1988-1989., p. B-10] **PEER REVIEWED** 

SKIN, EYE AND RESPIRATORY IRRITATIONS: 

 ... May produce irritation of the nasal mucous membranes, the respiratory 

 tract, and eyes. /Boron compounds/ [Sittig, M. Handbook of Toxic and 

 Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes 

 Data Corporation, 1985., p. 138] **PEER REVIEWED** 

MEDICAL SURVEILLANCE: 

 No specific considerations are needed for boric acid or borates except for 

 general health and liver and kidney function. /Boric acid and borates/ 

 [Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 

 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985., p. 139] 

 **PEER REVIEWED** 

TOXICITY SUMMARY: 

 IDENTIFICATION: (Elemental boron exists as a solid at room temperature, 

 either as black monoclinic crystals or as a yellow or brown amorphous 

 powder when impure). It is a naturally occurring element that is found in 

 the form of borates in the oceans, sedimentary rocks, coal, shale, and 

 some soils. Boron enters the environment mainly through the weathering of 

 rocks, boric acid volatilization from seawater, and volcanic activity. 

 Boron is also released from anthropogenic sources to a lesser extent. 

 These sources include agricultural, refuse, and fuel wood burning, power 

 generation using coal and oil, glass product manufacture, use of 

 borates/perborates in the home and industry, borate mining/processing, 

 leaching of treated wood/paper, and sewage/sludge disposal. HUMAN 

 EXPOSURE: Only a few human studies have been conducted to assess health 

 effects associated with exposure to boron compounds. The available data 

 show that exposure is associated with short-term irritant effects on the 

 upper respiratory tract, nasopharynx, and eye. These effects, however, 

 appear to be short-term and reversible. The sole long-term (7-year) 

 follow-up study failed to identify any long-term health effects. No 

 studies have been identified that assess reproductive outcomes. Based on 

 the lack of human data and the limited animal data, boron is not 

 classifiable as to its human carcinogenicity. ANIMAL STUDIES: Data 

 regarding developmental and reproductive toxicity show that lower fetal 

 body weight in rats is the critical effect. As dose level increases, the 

 effects seen include: further rib effects and testicular pathology in the 

 rat, decreased fetal body weight and increased fetal cardiovascular 

 malformations in the rabbit, and severe testicular pathology in the rat; 

 testicular atrophy and sterility in the rat; reduced fetal body weight in 

 the mouse. Animal studies on mice and rats showed no evidence of 

 carcinogenicity of boric acid. /Boron and Boron compounds/ [World Health 

 Organization/International Programme on Chemical Safety. Environmental 

 Health Criteria 204. Boron pp. 1-10 (1998)] **PEER REVIEWED** 

SKIN, EYE AND RESPIRATORY IRRITATIONS: 

 ... May produce irritation of the nasal mucous membranes, the respiratory 

 tract, and eyes. /Boron compounds/ [Sittig, M. Handbook of Toxic and 

 Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes 

 Data Corporation, 1985., p. 138] **PEER REVIEWED** 

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The following information was generated from the 

Hazardous Substances Data Bank (HSDB), 

a database of the National Library of Medicine's TOXNET system 

(http://toxnet.nlm.nih.gov) on October 27, 2009. 

Query: The chemical name cadmium was identified. 

The following terms were added from ChemIDplus: 

kadmium 

colloidal cadmium 

cadmium compounds 

CAS Registry Number: 7440-43-9 

1 

NAME: CADMIUM, ELEMENTAL 

RN: 7440-43-9 

NOTE: 

 This record contains information for cadmium in its zero valence state 

 only. For general toxicity and environmental fate of cadmium ions and 

 cadmium compounds, refer to the CADMIUM COMPOUNDS record; for 

 compound-specific information, to the appropriate individual record, e.g., 

 cadmium sulfate, cadmium chloride, etc. 

HUMAN HEALTH EFFECTS: 

EVIDENCE FOR CARCINOGENICITY: 

 Evaluation: There is sufficient evidence in humans for the carcinogenicity 

 of cadmium and cadmium compounds. There is sufficient evidence in 

 experimental animals for the carcinogenicity of cadmium compounds. There 

 is limited evidence in experimental animals for the carcinogenicity of 

 cadmium metal. In making the overall evaluation, the Working Group took 

 into consideration the evidence that ionic cadmium causes genotoxic 

 effects in a variety of types of eukaryotic cells, including human cells. 

 Overall evaluation: Cadmium and cadmium compounds are carcinogenic to 

 humans (Group 1). /Cadmium and cadmium compounds/ [IARC. Monographs on the 

 Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World 

 Health Organization, International Agency for Research on Cancer, 

 1972-PRESENT. (Multivolume work)., p. 58 210 (1993)] **PEER REVIEWED** 

 CLASSIFICATION: B1; probable human carcinogen. BASIS FOR CLASSIFICATION: 

 Limited evidence from occupational epidemiologic studies of cadmium is 

 consistent across investigators and study populations. There is sufficient 

 evidence of carcinogenicity in rats and mice by inhalation and 

 intramuscular and subcutaneous injection. Seven studies in rats and mice 

 wherein cadmium salts (acetate, sulfate, chloride) were administered 

 orally have shown no evidence of carcinogenic response. HUMAN 

 CARCINOGENICITY DATA: Limited. [U.S. Environmental Protection Agency's 

 Integrated Risk Information System (IRIS) on Cadmium (7440-43-9) from the 

 National Library of Medicine's TOXNET System, March 6, 1995] **PEER 

 REVIEWED** 

 A2; Suspected human carcinogen. /Cadmium and compounds, as Cd/ [American 

 Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold 

 Limit Values for Chemical Substances and Physical Agents and Biological 

 Exposure Indices. Cincinnati, OH, 2008, p. 16] **QC REVIEWED** 

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 Cadmium and Cadmium Compounds: known to be human carcinogens. 

 [DHHS/National Toxicology Program; Eleventh Report on Carcinogens: Cadmium 

 and Cadmium Compounds (January 2005). Available from, as of July 31, 2009: 

 http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s028cadm.pdf ] **QC 

 REVIEWED** 

HUMAN TOXICITY EXCERPTS: 

 In a retrospective study, 311 male workers in an alkaline battery factory 

 were evaluated for cadmium exposure. Workers were exposed to > 50 ug/cu 

 m for 1 - 35 years. Hypertension (defined by average blood pressure > 

 160/95 over a 5 year period) was noted in 23% of workers over 40. The 

 duration of employment correlated with the degree of hypertension among 

 age-matched groups of workers when compared to normotensives. In this 

 study laborers were exposed to levels that exceed 50 ug cadmium/cu m, 

 while today's workers are exposed to air levels averaging 10 ug cadmium/cu 

 m. [Engvall J, Perk J; Arch Env Health 40 (3): 185-90 (1985)] **PEER 

 REVIEWED** 

 The chief chronic pulmonary effects of cadmium are ... centrilobular 

 emphysema and bronchitis resulting from several years of occupational 

 exposure to cadmium oxide fumes, cadmium oxide dust, and cadmium pigment 

 dust. [USEPA; Health Assessment Document: Cadmium p.1-11 (1981) 

 EPA-600/8-81-023] **PEER REVIEWED** 

 Two hundred forty male and female workers in a battery factory along with 

 87 unexposed male controls were studied to determine the excretion of 

 beta(2)-microglobulin. The exposed workers were employed in the department 

 where materials for battery electrodes were made (material plant) or where 

 the electrodes and batteries were assembled (assembly plant). ... 

 Diagnosis of proteinuria was made in those whose microglobulin excretion 

 was greater than the upper 95% confidence limit of the normal 

 concentration in the urine; ... this was not considered necessarily to be 

 a clinically significant proteinuria. There was an increased incidence of 

 microglobulinuria in the exposed group. In the unexposed controls, 3.4% 

 had microglobulinuria. In the assembly plant, women had a 2.3% incidence 

 of this type of proteinuria and men had a 25% incidence. The men who 

 worked in the material plant had a 52% incidence of microglobulinuria. 

 These incidences in male workers were significantly different from control 

 incidences at (p < 0.001); differences in incidences between female 

 workers and controls were not significant. The 2.3% incidence among 

 working women represents one case of microglobulinuria among 41 women. Yet 

 15 of the women had been exposed for more than 5 years. The lower rate of 

 microglobulinuria among women might in part reflect a lower smoking rate; 

 of the 13 women whose smoking habits were known, 5 were smokers. 

 Nonsmoking cadmium exposed workers had a lower prevalence of the defined 

 proteinuria than smoking cadmium exposed workers. Nine of the workers were 

 separately treated in the study because they were from Yugoslavia, where 

 tubular proteinuria is endemic (Balkan nephropathy); two of them were 

 found to excrete increased amounts of microglobulin. In the 185 employees 

 that worked continuously with cadmium, the prevalence of microglobulinuria 

 increased with exposure time. [NIOSH; Criteria Document: Cadmium p.23 

 (1976) DHEW Pub. NIOSH 76-192] **PEER REVIEWED** 

 Renal tubular dysfunction was assessed in 102 individuals (36% women, 64% 

 men) with greater than 5 years employment in cadmium battery production in 

 an alkaline battery factory. A control group consisted of 53 individuals 

 not involved in cadmium battery production, and another 32 individuals 

 working in a cotton factory. Blood cadmium (Cd-B), urine cadmium (Cd-U), 

 retinol binding protein (RBP), B2-microglobulin (B2-M), and aminoaciduria 

 were determined before the work shift. Wilcoxin's rank sum test was used 

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 to assess differences between the control and study groups. Cd-B and Cd-U 

 were higher for subjects working in Cd battery production (Cd-B= 7.5 to 49 

 ug/l; Cd-U= 5.5 to 36 ug/l) than for those employed at the cotton factory 

 or in work not related to Cd battery production at the alkaline battery 

 factory (Cd-B= 4.8 ug/l; Cd-U= 1.0 ug/l). Urinary excretion of B2-M and 

 RBP was significantly elevated depending on specific work location in the 

 factory) in 20% of workers involved with Cd battery production. A high 

 correlation coefficient (r= 0.85) was obtained for Cd-B and Cd-U values, 

 possibly because Cd-U becomes an indicator of current Cd exposure when Cd 

 exposure is great. Correlation between Cd-U and excretion of B2-M and RBP 

 (r= 0.52 and 0.55, respectively) was also greater than previous reports 

 and possibly indicative of high Cd exposure levels. [Jakubowski M et al; 

 Int Arch Occup Environ Health 59 (6): 567-77 (1987)] **PEER REVIEWED** 

 Food and Environmental Agents: Effect on Breast-Feeding: Reported Sign or 

 Symptom in Infant or Effect on Lactation: Cadmium: None Reported. /from 

 Table 7/ [Report of the American Academy of Pediatrics Committee on Drugs 

 in Pediatrics 93 (1): 142 (1994)] **PEER REVIEWED** 

 The consequence of excessive inhalation of cadmium fumes and dusts is loss 

 of ventilatory capacity, with a corresponding increase in residual lung 

 volume. Dyspnea is the most frequent complaint of patients with cadmium 

 induced lung disease. The pathogenesis of cadmium-induced emphysema and 

 pulmonary fibrosis is not well understood; however, cadmium specifically 

 inhibits the synthesis of plasma alpha 1-antitrypsin, and there is an 

 association between severe alpha 1-antitrypsin deficiency of genetic 

 origin and emphysema in human beings. [Hardman, J.G., L.E. Limbird, P.B. 

 Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The 

 Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 

 1996., p. 1663] **PEER REVIEWED** 

 FUMES & DUST OF CADMIUM & ITS CMPD ARE VERY TOXIC. /CADMIUM, 

 ALLOYS, COMPOUNDS/ [International Labour Office. Encyclopedia of 

 Occupational Health and Safety. Volumes I and II. New York: McGraw-Hill 

 Book Co., 1971., p. 233] **PEER REVIEWED** 

 ... EVIDENCE OF GONADAL EFFECTS FROM CADMIUM; MICROSCOPIC CHANGES 

 CONSISTING OF DEPRESSION & MATURATION OF SPERMATOCYTES, ASSOC WITH 

 HIGH LEVELS OF CADMIUM, WERE FOUND IN TESTES OF MEN EXPOSED TO CADMIUM 

 FUME. /CADMIUM FUME/ [Clayton, G. D. and F. E. Clayton (eds.). Patty's 

 Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. 

 New York: John Wiley Sons, 1981-1982., p. 1569] **PEER REVIEWED** 

 CADMIUM AND ITS SALTS ARE HIGHLY TOXIC. ... INHALATION (DUST OR FUMES): 

 THROAT DRYNESS, COUGH, HEADACHE, VOMITING, CHEST PAIN, EXTREME 

 RESTLESSNESS & IRRITABILITY, PNEUMONITIS, POSSIBLY BRONCHOPNEUMONIA. 

 /CADMIUM AND ITS SALTS/ [The Merck Index. 10th ed. Rahway, New Jersey: 

 Merck Co., Inc., 1983., p. 223] **PEER REVIEWED** 

 Acute poisoning may result from inhalation of cadmium dusts & fumes 

 ... & from ingestion of cadmium salts. When swallowed, cadmium 

 compounds are much less lethal than when inhaled, in part because they 

 induce vomiting & ... are not retained. Although as little as 10-20 mg 

 of sol cadmium salts have produced severe toxic symptoms when ingested, 

 death probably requires several hundred milligrams by oral route. /Cadmium 

 and cadmium salts/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical 

 Toxicology of Commercial Products. 5th ed. Baltimore: Williams and 

 Wilkins, 1984., p. III-78] **PEER REVIEWED** 

 Inhalation of cadmium dusts, salts & fume over a number of ... years 

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 result in chronic cadmium poisoning, a disease characterized by 

 distinctive, nonhypertrophic emphysema with or without renal tubular 

 injury, in which urinary excretion of a protein of molecular wt of 20,000 

 to 30,000 occurs. ... Further inhalation overexposure results in 

 irreversible renal tubular damage, which may progress into complete 

 Fanconi syndrome with decreased tubular reabsorption of proteins, glucose, 

 amino acids, calcium, phosphorus, & with decreased ability to acidify 

 & concentrate the urine. Other ... toxic effects include anemia, 

 eosinophilia, anosmia, chronic rhinitis, yellow discoloration of teeth, 

 & bone changes. /Cadmium and cadmium cmpd/ [American Conference of 

 Governmental Industrial Hygienists. Documentation of the Threshold Limit 

 Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American 

 Conference of Governmental Industrial Hygienists, 1986., p. 87] **PEER 

 REVIEWED** 

 CADMIUM IS APPARENTLY NOT RESPONSIBLE FOR CASES OF PROSTATIC OR OTHER 

 CANCER OBSERVED IN MEN WORKING IN CADMIUM DUST. [MALCOLM D; ANN OCCUP HYG: 

 15 (1): 33 (1972)] **PEER REVIEWED** 

SKIN, EYE AND RESPIRATORY IRRITATIONS: 

 It is irritating to the nose and throat ... /From table/ [Sullivan, J.B. 

 Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical 

 Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 

 1992., p. 691] **PEER REVIEWED** 

MEDICAL SURVEILLANCE: 

 Initial medical examination: a complete history and physical examination 

 detect pre-existing conditions that might place the exposed employee at 

 increased risk, and to establish a baseline for future health monitoring. 

 Examination of the respiratory system, liver, kidneys, prostate, and blood 

 should be stressed. Since kidney damage has been observed in humans 

 exposed to cadmium, a urinalysis should be obtained to include, at 

 minimum: specific gravity, albumin, glucose, and a microscopic 

 /examination of the/ centrifuged sediment. In addition, the urine should 

 be examined for low molecular weight proteins by use of 3% sulfosalicylic 

 acid or other acceptable techniques. A 14 x 17 in roentgenogram should be 

 obtained as cadmium causes human lung damage. Surveillance of the lungs is 

 recommended. A profile of liver function should be obtained by utilizing a 

 medically acceptable array of biochemical tests.Since cadmium may cause 

 liver damage. FVC and FEV (1 sec): cadmium is reported to cause decreased 

 pulmonary function. Therefore periodic surveillance is recommended. 

 Medical examinations should be repeated annually, except that X-ray is 

 considered necessary only when indicated by pulmonary function tests or by 

 symptoms of respiratory disease. Urine protein measurements should be 

 available every four months. /Cadmium dust (as cadmium)/ [Mackison, F. W., 

 R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational 

 Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 

 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 

 2] **PEER REVIEWED** 

 Environmental monitoring records shall be maintained for at least 20 

 years. These records shall include methods of sampling and analysis used, 

 types of respiratory protection used, and TWA and ceiling concentrations 

 found. Each employee shall have made available to them information on 

 their own environmental exposures. Environmental records shall be 

 available to designated representatives of the Secretary of Labor, and the 

 Secretary of /Health and Human Services/. Pertinent medical records shall 

 be retained for 20 years after the last occupational exposure to cadmium. 

 Records of environmental exposures applicable to the employee should be 

 included in that employee's medical records. These medical records shall 

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 be made available to the designated medical representatives of the 

 Secretary of Labor & of /Health and Human Services/, of the employer, 

 and of the employee or former employee. /Cadmium cmpd/ [NIOSH; Criteria 

 Document: Cadmium p.5 (1976) DHEW Pub. NIOSH 76-192] **PEER REVIEWED** 

 The assessment of cadmium exposure can be accomplished through measurement 

 of cadmium. Studies assessing correlation of blood levels with 

 occupational exposure found that blood levels correlate with recent 

 exposures, and not well with chronic exposure or assessment of total body 

 burden. Whole Blood Reference ranges: Normal - non-occupational exposure 

 levels range from 0.4 to 1.0 ug/l for nonsmokers and up to 4.5 ug/l for 

 smokers; Exposed - BEI (sampling time is not critical): 5 ug/l; Toxic - 

 levels greater than 10 ug/l have been associated with worker toxicity such 

 as renal dysfunction. Serum or Plasma Reference Ranges: Normal - 0.5 to 2 

 ug/l; Exposed - not established; Toxic - not established. Urine Reference 

 ranges: Normal - non-occupational exposure levels range from 0.02 to 4.5 

 ug/l; Exposed - BEI (sampling time is not critical): 5 ug/g creatinine; 

 Toxic - Several studies have indicated that urinary levels greater than 10 

 ug/g creatinine or 10 ug/l in workers have been associated with an 

 increased incidence of renal dysfunction. /Cadmium/ [Ryan, R.P., C.E. 

 Terry (eds.). Toxicology Desk Reference 4th ed. Volumes 1-3. Taylor & 

 Francis, Washington, D.C. 1997., p. 525] **PEER REVIEWED** 

 Respiratory Symptom Questionnaires: Questionnaires have been published by 

 the American Thoracic Society (ATS) and the British Medical Research 

 Council. These questionnaires have been found to be useful in 

 identification of people with chronic bronchitis. however certain 

 pulmonary function tests such as FEV1 (see pulmonary function test 

 section) have been found to be better predictors of chronic airflow 

 obstruction. /Cadmium/ [Ryan, R.P., C.E. Terry (eds.). Toxicology Desk 

 Reference 4th ed. Volumes 1-3. Taylor & Francis, Washington, D.C. 

 1997., p. 529] **PEER REVIEWED** 

 Chest Radiography: This test is widely used for assessing pulmonary 

 disease. Chest radiographs have been found to be useful for detection of 

 early lung cancer in asymptomatic people, especially for detection of 

 peripheral tumors such as adenocarcinomas. However, even though OSHA 

 mandates this test for exposure to some toxicants such as asbestos, there 

 are conflicting views on its efficacy in detection of pulmonary disease. 

 /Cadmium/ [Ryan, R.P., C.E. Terry (eds.). Toxicology Desk Reference 4th 

 ed. Volumes 1-3. Taylor & Francis, Washington, D.C. 1997., p. 529] 

 **PEER REVIEWED** 

 Pulmonary Function Tests: The tests that have been found to be practical 

 for population monitoring include: Spirometry and expiratory flow-volume 

 curves; Determination of lung volumes; Single-breath nitrogen washout; 

 Inhalation challenges tests; Serial measurements of peak expiratory flow; 

 Exercise testing. /Cadmium/ [Ryan, R.P., C.E. Terry (eds.). Toxicology 

 Desk Reference 4th ed. Volumes 1-3. Taylor & Francis, Washington, 

 D.C. 1997., p. 529] **PEER REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 OCCUPATIONAL EXPOSURE: EXPOSURE OCCURS PRIMARILY IN SMELTING & 

 REFINING ZINC, LEAD & COPPER ORES CONTAINING CADMIUM, SPRAYING CADMIUM 

 CONTAINING PIGMENTS, PROCESSING SCRAP CONTAINING CADMIUM, ETC. /CADMIUM, 

 ALLOYS, COMPOUNDS/ [International Labour Office. Encyclopedia of 

 Occupational Health and Safety. Volumes I and II. New York: McGraw-Hill 

 Book Co., 1971., p. 233] **PEER REVIEWED** 

 The major route of exposure to cadmium for the non-smoking general 

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 population is via food ... Tobacco is an important source of cadmium 

 uptake in smokers. [WHO; Environmental Health Criteria 134: Cadmium p.18 

 (1992)] **PEER REVIEWED** 

BODY BURDEN: 

 /IN MAN/ ABOUT HALF OF TOTAL BODY BURDEN IS FOUND IN LIVER & KIDNEYS 

 ... CADMIUM IN THESE ORGANS IS MAINLY BOUND TO A LOW MOLECULAR WEIGHT 

 PROTEIN, IN FORM OF A METALLOTHIONEIN ... [IARC. Monographs on the 

 Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World 

 Health Organization, International Agency for Research on Cancer, 

 1972-PRESENT. (Multivolume work)., p. V2 90 (1973)] **PEER REVIEWED** 

 The body burden of cadmium in a 50 yr old adult in the US is about 30 mg. 

 [Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman 

 (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 

 9th ed. New York, NY: McGraw-Hill, 1996., p. 1662] **PEER REVIEWED** 

AVERAGE DAILY INTAKE: 

 50 ug [Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. 

 Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of 

 Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1662] **PEER 

 REVIEWED** 

 Average daily intakes from food in most areas not polluted with cadmium 

 are between 10-40 ug. In polluted areas it has been found to be several 

 hundred ug/day. [WHO; Environmental Health Criteria 134: Cadmium p.22 

 (1992)] **PEER REVIEWED** 

MINIMUM FATAL DOSE LEVEL: 

 Average concentrations responsible for fatal cases have been estimated at 

 50 mg/cu m and 40 mg/cu m, both for exposures of 1 hr; and 9 mg/cu m for 5 

 hr. [American Conference of Governmental Industrial Hygienists, Inc. 

 Documentation of the Threshold Limit Values and Biological Exposure 

 Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 191] 

 **PEER REVIEWED** 

EVIDENCE FOR CARCINOGENICITY: 

 Evaluation: There is sufficient evidence in humans for the carcinogenicity 

 of cadmium and cadmium compounds. There is sufficient evidence in 

 experimental animals for the carcinogenicity of cadmium compounds. There 

 is limited evidence in experimental animals for the carcinogenicity of 

 cadmium metal. In making the overall evaluation, the Working Group took 

 into consideration the evidence that ionic cadmium causes genotoxic 

 effects in a variety of types of eukaryotic cells, including human cells. 

 Overall evaluation: Cadmium and cadmium compounds are carcinogenic to 

 humans (Group 1). /Cadmium and cadmium compounds/ [IARC. Monographs on the 

 Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World 

 Health Organization, International Agency for Research on Cancer, 

 1972-PRESENT. (Multivolume work)., p. 58 210 (1993)] **PEER REVIEWED** 

 CLASSIFICATION: B1; probable human carcinogen. BASIS FOR CLASSIFICATION: 

 Limited evidence from occupational epidemiologic studies of cadmium is 

 consistent across investigators and study populations. There is sufficient 

 evidence of carcinogenicity in rats and mice by inhalation and 

 intramuscular and subcutaneous injection. Seven studies in rats and mice 

 wherein cadmium salts (acetate, sulfate, chloride) were administered 

 orally have shown no evidence of carcinogenic response. HUMAN 

 CARCINOGENICITY DATA: Limited. [U.S. Environmental Protection Agency's 

 Integrated Risk Information System (IRIS) on Cadmium (7440-43-9) from the 

 National Library of Medicine's TOXNET System, March 6, 1995] **PEER 

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 REVIEWED** 

 A2; Suspected human carcinogen. /Cadmium and compounds, as Cd/ [American 

 Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold 

 Limit Values for Chemical Substances and Physical Agents and Biological 

 Exposure Indices. Cincinnati, OH, 2008, p. 16] **QC REVIEWED** 

 Cadmium and Cadmium Compounds: known to be human carcinogens. 

 [DHHS/National Toxicology Program; Eleventh Report on Carcinogens: Cadmium 

 and Cadmium Compounds (January 2005). Available from, as of July 31, 2009: 

 http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s028cadm.pdf ] **QC 

 REVIEWED** 

MINIMUM FATAL DOSE LEVEL: 

 Average concentrations responsible for fatal cases have been estimated at 

 50 mg/cu m and 40 mg/cu m, both for exposures of 1 hr; and 9 mg/cu m for 5 

 hr. [American Conference of Governmental Industrial Hygienists, Inc. 

 Documentation of the Threshold Limit Values and Biological Exposure 

 Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 191] 

 **PEER REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 OCCUPATIONAL EXPOSURE: EXPOSURE OCCURS PRIMARILY IN SMELTING & 

 REFINING ZINC, LEAD & COPPER ORES CONTAINING CADMIUM, SPRAYING CADMIUM 

 CONTAINING PIGMENTS, PROCESSING SCRAP CONTAINING CADMIUM, ETC. /CADMIUM, 

 ALLOYS, COMPOUNDS/ [International Labour Office. Encyclopedia of 

 Occupational Health and Safety. Volumes I and II. New York: McGraw-Hill 

 Book Co., 1971., p. 233] **PEER REVIEWED** 

 The major route of exposure to cadmium for the non-smoking general 

 population is via food ... Tobacco is an important source of cadmium 

 uptake in smokers. [WHO; Environmental Health Criteria 134: Cadmium p.18 

 (1992)] **PEER REVIEWED** 

BODY BURDEN: 

 /IN MAN/ ABOUT HALF OF TOTAL BODY BURDEN IS FOUND IN LIVER & KIDNEYS 

 ... CADMIUM IN THESE ORGANS IS MAINLY BOUND TO A LOW MOLECULAR WEIGHT 

 PROTEIN, IN FORM OF A METALLOTHIONEIN ... [IARC. Monographs on the 

 Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World 

 Health Organization, International Agency for Research on Cancer, 

 1972-PRESENT. (Multivolume work)., p. V2 90 (1973)] **PEER REVIEWED** 

 The body burden of cadmium in a 50 yr old adult in the US is about 30 mg. 

 [Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman 

 (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 

 9th ed. New York, NY: McGraw-Hill, 1996., p. 1662] **PEER REVIEWED** 

AVERAGE DAILY INTAKE: 

 50 ug [Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. 

 Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of 

 Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1662] **PEER 

 REVIEWED** 

 Average daily intakes from food in most areas not polluted with cadmium 

 are between 10-40 ug. In polluted areas it has been found to be several 

 hundred ug/day. [WHO; Environmental Health Criteria 134: Cadmium p.22 

 (1992)] **PEER REVIEWED** 

SKIN, EYE AND RESPIRATORY IRRITATIONS: 

 It is irritating to the nose and throat ... /From table/ [Sullivan, J.B. 

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 Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical 

 Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 

 1992., p. 691] **PEER REVIEWED** 

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The following information was generated from the 

Hazardous Substances Data Bank (HSDB), 

a database of the National Library of Medicine's TOXNET system 

(http://toxnet.nlm.nih.gov) on October 27, 2009. 

Query: The chemical name chromium was identified. 

The following terms were added from ChemIDplus: 

chrome 

CAS Registry Number: 7440-47-3 

1 

NAME: CHROMIUM, ELEMENTAL 

RN: 7440-47-3 

NOTE: 

 This record contains information specific to the title compound. Users 

 with an interest in this substance are strongly encouraged to retrieve the 

 Chromium Compounds record, which has additional information on toxicity 

 and environmental fate of chromium ions and compounds. 

HUMAN HEALTH EFFECTS: 

EVIDENCE FOR CARCINOGENICITY: 

 A4: Not classifiable as a human carcinogen. /Metal and Cr(III) compounds, 

 as Cr/ [American Conference of Governmental Industrial Hygienists TLVs and 

 BEIs. Threshold Limit Values for Chemical Substances and Physical Agents 

 and Biological Exposure Indices. Cincinnati, OH, 2008, p. 20] **QC 

 REVIEWED** 

 Chromium Hexavalent Compounds: known to be human carcinogens. 

 [DHHS/National Toxicology Program; Eleventh Report on Carcinogens: 

 Selenium Chromium Hexavalent Compounds (January 2005). Available from, as 

 of July 31, 2009: 

 http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s045chro.pdf ] **QC 

 REVIEWED** 

HUMAN TOXICITY EXCERPTS: 

 CHROMIUM METAL ... APPEARS TO BE INNOCUOUS. ... NO VISUAL DISTURBANCES IN 

 PATIENTS PURPORTEDLY POISONED BY CHROMIUM (CR) BUT ... NARROWING OF 

 RETINAL ARTERIES & PALLOR & INDISTINCTNESS OF PAPILLA IN THREE 

 CASES, & RETINAL HEMORRHAGE IN A FOURTH CASE ... /REPORTED/. [Grant, 

 W. M. Toxicology of the Eye. 2nd ed. Springfield, Illinois: Charles C. 

 Thomas, 1974., p. 290] **PEER REVIEWED** 

 Liver tissue was contaminated with 0.02 and 11 ppm chromium (Cr) from 

 stainless steel scalpels and needles, while a blood sample drawn with a 

 stainless steel needle was contaminated with 85 ppb chromium (Cr). 

 [Versieck JMJ, Speecke ABH; In Nuclear Activation Techniques in the Life 

 Sciences by Int'l Atomic Energy Agency p.39-49 (1972) as cited in Nat'l 

 Research Council Canada; Effects of Chromium in the Canadian Envir p.118 

 (1976) NRCC No.15017] **PEER REVIEWED** 

 A total of 39 electric welders exposed to chromium ... were compared with 

 18 controls standardized for age, sex, and smoking habits with respect to 

 the frequency of sister chromatid exchanges and DNA strand breakage and 

 cross-linking (measured by the method of alkaline filter elution) in their 

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 blood lymphocytes. A significant correlation was found between the 

 frequency of SCEs and of individual DNA strand breakage versus the 

 concentration of chromium in the urine. [Clayton, G.D., F.E. Clayton 

 (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 

 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 

 1993-1994., p. 1981] **PEER REVIEWED** 

 ... 1879 male workers employed in a New Jersey chromium pigment factory 

 was conducted, with follow up from 1940 to 1982. For all malignant 

 neoplasms, 101 deaths were observed, and 108.8 were expected. For the 

 entire study group, no significant excess was observed for respiratory 

 cancer or cancer at other sites. [Clayton, G.D., F.E. Clayton (eds.) 

 Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: 

 Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., 

 p. 1980] **PEER REVIEWED** 

 EXPOSURE TO CHROMIUM METAL DOES NOT GIVE RISE TO PULMONARY FIBROSIS OR 

 PNEUMOCONIOSIS. [American Conference of Governmental Industrial 

 Hygienists, Inc. Documentation of the Threshold Limit Values and 

 Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: 

 ACGIH, 1991., p. 313] **PEER REVIEWED** 

 Symptoms /of exposure/: histologic fibrosis of lung /Chromium metal and 

 insoluble salts (as Cr)/ [NIOSH. Pocket Guide to Chemical Hazards. 5th 

 Printing/Revision. DHHS (NIOSH) Publ. No. 85-114. Washington, D.C.: U.S. 

 Dept. of Health and Human Services, NIOSH/Supt. of Documents, GPO, Sept. 

 1985., p. 83] **PEER REVIEWED** 

SKIN, EYE AND RESPIRATORY IRRITATIONS: 

 Chromium aerosols ... caused ... irritation to the upper respiratory 

 tract. /SRP: dusts or particulates/ [Waldbott GL; Health Effects of Envir 

 Poll p.201 (1973)] **PEER REVIEWED** 

 Chromium causes severe nasal irritation ... . [Arena, J.M. and Drew, R.H. 

 (eds.) Poisoning-Toxicology, Symptoms, Treatments. 5th ed. Springfield, 

 IL: Charles C. Thomas Publisher, 1986., p. 873] **PEER REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 Stainless steel use in mixing containers in the baking industries may be 

 the source of extraneous chromium in food. [Nat'l Research Council Canada; 

 Effects of Chromium in the Canadian Envir p.43 (976) NRCC No.15017] **PEER 

 REVIEWED** 

EVIDENCE FOR CARCINOGENICITY: 

 A4: Not classifiable as a human carcinogen. /Metal and Cr(III) compounds, 

 as Cr/ [American Conference of Governmental Industrial Hygienists TLVs and 

 BEIs. Threshold Limit Values for Chemical Substances and Physical Agents 

 and Biological Exposure Indices. Cincinnati, OH, 2008, p. 20] **QC 

 REVIEWED** 

 Chromium Hexavalent Compounds: known to be human carcinogens. 

 [DHHS/National Toxicology Program; Eleventh Report on Carcinogens: 

 Selenium Chromium Hexavalent Compounds (January 2005). Available from, as 

 of July 31, 2009: 

 http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s045chro.pdf ] **QC 

 REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 Stainless steel use in mixing containers in the baking industries may be 

 the source of extraneous chromium in food. [Nat'l Research Council Canada; 

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 Effects of Chromium in the Canadian Envir p.43 (976) NRCC No.15017] **PEER 

 REVIEWED** 

SKIN, EYE AND RESPIRATORY IRRITATIONS: 

 Chromium aerosols ... caused ... irritation to the upper respiratory 

 tract. /SRP: dusts or particulates/ [Waldbott GL; Health Effects of Envir 

 Poll p.201 (1973)] **PEER REVIEWED** 

 Chromium causes severe nasal irritation ... . [Arena, J.M. and Drew, R.H. 

 (eds.) Poisoning-Toxicology, Symptoms, Treatments. 5th ed. Springfield, 

 IL: Charles C. Thomas Publisher, 1986., p. 873] **PEER REVIEWED** 

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The following information was generated from the 

Hazardous Substances Data Bank (HSDB), 

a database of the National Library of Medicine's TOXNET system 

(http://toxnet.nlm.nih.gov) on October 27, 2009. 

Query: The chemical name cobalt was identified. 

The following terms were added from ChemIDplus: 

super cobalt 

aquacat 

CAS Registry Number: 7440-48-4 

1 

NAME: COBALT, ELEMENTAL 

RN: 7440-48-4 

NOTE: 

 This record contains information for cobalt in its zero valence state 

 only. For general toxicity and environmental fate of cobalt ions and 

 cobalt compounds, refer to the COBALT COMPOUNDS record; for compound 

 specific information, refer to the appropriate individual records, e.g., 

 cobalt acetate, cobalt succinate, etc. For information on the radiological 

 aspects of cobalt and its compounds, refer to the COBALT, RADIOACTIVE 

 record. For general toxicological, safety and handling, and environmental 

 information on ionizing radiation emitted from chemical sources including 

 uranium, refer to the IONIZING RADIATION RECORD. 

HUMAN HEALTH EFFECTS: 

EVIDENCE FOR CARCINOGENICITY: 

 A3: Confirmed animal carcinogen with unknown relevance to humans. /Cobalt 

 and inorganic compounds, as Co/ [American Conference of Governmental 

 Industrial Hygienists TLVs and BEIs. Threshold Limit Values for Chemical 

 Substances and Physical Agents and Biological Exposure Indices. 

 Cincinnati, OH, 2008, p. 21] **QC REVIEWED** 

HUMAN TOXICITY EXCERPTS: 

 /OTHER TOXICITY INFORMATION/ In the industry, the potential for exposure 

 to cobalt metal dust is particularly important during the production of 

 cobalt powder and the processing and use of hard metals and other 

 cobalt-containing alloys. The different adverse health effects reported in 

 these workers are reviewed. One of the main target organs is the 

 respiratory tract, and this article concentrates on the lung parenchymal 

 reactions induced by cobalt-containing dust. Clinical and epidemiological 

 data indicate that this manifestation is rarely, if ever, induced by pure 

 cobalt metal dust alone, but requires the concomitant inhalation of other 

 compounds such as tungsten carbide in the hard metal industry (hard metal 

 disease). [Lison D; Crit Rev Toxicol. 26 (6): 585-6 16 (1996)] **PEER 

 REVIEWED** 

 /CASE REPORTS/ Cases of industrial dermatitis occurring chiefly in metal 

 room of a cemented carbide tool plant were examined ... Eruption, of 

 erythematous papular type, was localized in most cases to points of 

 friction such as ankles, elbow flexures and sides of neck. Patch tests 

 were positive to metallic cobalt powder ... . [Browning, E. Toxicity of 

 Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 

 139] **PEER REVIEWED** 

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 /CASE REPORTS/ Workers exposed to cobalt powder during the grinding and 

 manufacturing of tungsten carbide /were examined/. ... A progressive 

 interstitial lung disease /was/ manifested by 12 workers; 8 cases were 

 fatal, and microscopic exam of the lung showed interstitial infiltration 

 and fibrosis. The exposure periods for these 12 workers ranged from 1 

 month to 28 yr with concn of cobalt exceeding 0.1 mg/cu m. ... In addition 

 to 12 cases of lung fibrosis a further respiratory disease, characterized 

 by cough, wheezing and shortness of breath /was described/. [Friberg, L., 

 Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the 

 Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science 

 Publishers B.V., 1986., p. V2 221] **PEER REVIEWED** 

 /SIGNS AND SYMPTOMS/ A study described pulmonary changes in 8 of 247 

 workers; exposure levels measured in the plant were 0.8-12 mg of cobalt/cu 

 m of air. The workers complained of nausea, abdominal pains, loss of 

 appetite, cough, and a deterioration of the sense of smell. Some also had 

 decreased hemoglobin levels and red blood cell counts, liver and spleen 

 enlargement, and dermatitis. After dust control measures were implemented, 

 the levels of airborne cobalt decreased to 0.4-3.3 mg/cu m. Later, 117 

 workers were examined, and 35 (30%) had chronic bronchitis, 33 (29%) had 

 early fibrotic changes evident in chest radiographs, and 52 (44%) had 

 decreased blood pressure. Reasons for the increased incidence of pulmonary 

 changes at the lower exposure level were not given. Any number of factors 

 could have been involved, including the slowly progressive nature of 

 fibrosis in an aging workforce. [Kaplun ZS; Tsvetn Met 30: 42-8 (1957) as 

 cited in NIOSH; Criteria Document: Cobalt p.7 (1981) DHEW Pub. NIOSH 

 82-107] **PEER REVIEWED** 

 /SIGNS AND SYMPTOMS/ Several reports have ... described evidence of 

 bronchitis, emphysema, or asthma in workers exposed to cobalt in the hard 

 metal industry. Bronchitis was said to be more prevalent in workers 

 exposed to what were described only as large dust particles; 

 pneumoconiosis was said to have occurred more often after exposure to 

 dusts of smaller size. The asthmatic responses seem to represent a true 

 sensitization to cobalt. These persons developed a hacking or wheezy cough 

 within 1 mo to 1.7 yr of initial exposure to cobalt. One person also had 

 eczema. Recovery occurred when the workers left the work environment. One 

 worker remained on his job as a tool grinder, and he developed nodules 

 visible on chest radiographs 2.5 yr later. The others had no signs of 

 fibrosis. [NIOSH; Criteria Document: Cobalt p.9 (1981) DHEW Pub. NIOSH 

 82-107] **PEER REVIEWED** 

 /HUMAN EXPOSURE STUDIES/ The effect of hard metal dust containing cobalt 

 on pulmonary function was evaluated in a three part study. Fifteen healthy 

 young men, previously unexposed to hard metal dust, showed a significant 

 decrease (p < 0.05) in FVC after a 6 hr exposure to hard metal dust 

 containing cobalt at a mean concentration of 38 ug/cu m. There were no 

 significant correlations between decrease in forced vital capacity and the 

 hard metal dust or the cobalt concentrations. [Kusaka Y et al; Br J Ind 

 Med 43: 486-89 (1986)] **PEER REVIEWED** 

 /SIGNS AND SYMPTOMS/ In a cross-sectional examination of 42 workers 

 exposed to cobalt at an average concentration of 85 ug/cu m, no 

 significant decreases in ventilatory function were detected after 7 hr 

 exposure to hard metal dust. In a retrospective cohort analysis of 42 

 workers who had been exposed to cobalt at a mean concentration of 126 

 ug/cu m, the forced expiratory volume at 1 second was significantly (p < 

 0.05) decreased compared with matched controls. [Kusaka Y et al; Br J Ind 

 Med 43: 486-89 (1986)] **PEER REVIEWED** 

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 /CASE REPORTS/ ...Three cases of pneumoconiosis in tungsten carbide tool 

 industry where exposure to cobalt powder, oxide or salt, had varied 

 between 0.1 and 0.2 mg Co/cu m for 2.5-7 yr /are reported/. It was stated 

 that these 3 men were only workers with pneumoconiosis out of 1500 men 

 with similar exposure conditions. /cobalt powder, oxide or salt/ [Friberg, 

 L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the 

 Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science 

 Publishers B.V., 1986., p. V2 221] **PEER REVIEWED** 

 /SIGNS AND SYMPTOMS/ In the 1980s, investigators reported occupational 

 asthma and /interstitial lung disease (ILD)/ in diamond polishers exposed 

 to cobalt in the absence of /tungsten carbide (TC)/. Exposure occurred 

 during the use of discs whose cutting surface consisted of microdiamonds 

 cemented into very fine cobalt. Clinical features in the five patients 

 with ILD were similar to those reported in patients with ILD who had been 

 exposed in TC production. In the 5 cases reported, latencies ranged from 

 2-5 years and common symptoms included rhinitis, cough, chest tightness, 

 dyspnea, and weight loss. Crackles were found on physical exam. Diffuse 

 small nodules or a reticulonodular pattern with some predominance in the 

 lower zones was found on chest radiographs. Pulmonary function test 

 results showed restriction, and usually decreased diffusing capacity. 

 /Bronchoalveolar lavage (BAL)/, performed in 3 of the cases, showed 

 multinucleate giant cells in 2. Elevations in eosinophils occurred in 1 

 BAL specimen, while another showed T-cell lymphocytosis, with a 

 predominance of CD8+ cells. The third BAL specimen had a normal 

 differential cell distribution. Two BAL specimens were tested: 1 had an 

 elevated cobalt level and 1 did not. Pathologic exam of lung biopsy 

 specimens showed giant cell interstitial pneumonitis in two. The others 

 had fibrosing alveolitis, inflammatory infiltrates, or a combination of 

 fibrosis and inflammation. Four of the five were treated with prednisone 

 and 1 of those also had azathioprine. The clinical courses were 

 characterized by improvements in symptoms, lung function, and chest 

 radiographs when exposure ceased or was reduced. Interestingly, for those 

 who went back to work after the diagnosis was made, the disease waxed and 

 waned depending on conditions at the plant such as the adequacy of exhaust 

 ventilation. [Rom, W.N. (ed.). Environmental and Occupational Medicine. 

 2nd ed. Boston, MA: Little, Brown and Company, 1992., p. 795] **PEER 

 REVIEWED** 

 /SIGNS AND SYMPTOMS/ Potential symptoms as a result of exposure /to cobalt 

 metal, fume, and dust (as Co)/: cough, dyspnea, decreased pulmonary 

 function; weight loss ... diffuse nodular fibrosis; respiratory 

 hypersensitivity. /Cobalt metal, fume, and dust (as Co)/ [NIOSH. Pocket 

 Guide to Chemical Hazards. 2nd Printing. DHHS (NIOSH) Publ. No. 85-114. 

 Washington, D.C.: U.S. Dept. of Health and Human Services, NIOSH/Supt. of 

 Documents, GPO, February 1987., p. 85] **PEER REVIEWED** 

 /SIGNS AND SYMPTOMS/ Interstitial lung disease attributed to cobalt not 

 alloyed to carbides of hard metals may induce cough, chest tightness, 

 dyspnea, weight loss, a severe restrictive defect, and a markedly 

 decreased diffusing capacity and may be accompanied by the presents of 

 multiple multinucleated giant cells in the bronchoalveolar lavage. This 

 condition may show a rapidly fatal progression. [Ellenhorn, M.J., S. 

 Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: 

 Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: 

 Williams and Wilkins, 1997., p. 1554] **PEER REVIEWED** 

 /SIGNS AND SYMPTOMS/ Even at fairly low cobalt concentrations, inhalation 

 may lead to irritation of the mucous membranes in the respiratory tract. 

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 Lung function tests may reveal signs of obstructive lung disease. 

 Inhalation of cobalt in hard metal processing may cause hard metal lung 

 disease, which is a severe type of pneumoconiosis. The disease progresses 

 from chronic airway obstruction to interstitial lung fibrosis, causing 

 increasingly severe dyspnea. [Chang, L.W. (ed.). Toxicology of Metals. 

 Boca Raton, FL: Lewis Publishers, 1996, p. 99] **PEER REVIEWED** 

 /OTHER TOXICITY INFORMATION/ ...Sensitization may drive a granulomatous 

 reaction. [Klaassen, C.D. (ed). Casarett and Doull's Toxicology. The 

 Basic Science of Poisons. 6th ed. New York, NY: McGraw-Hill, 2001., p. 

 666] **PEER REVIEWED** 

 /OTHER TOXICITY INFORMATION/ Pulmonary effects have been regarded as the 

 major occupational problem in relation to cobalt, particularly in the 

 hard-metal industry where cobalt-containing dust is generated. Two types 

 of lung lesions may develop - interstitial fibrosis (so-called 'hard metal 

 pneumoconiosis') and occupational asthma. Hard-metal pneumoconiosis is a 

 severe and progressive type of pneumoconiosis which may develop after 

 several years of exposure to cobalt-containing dust at concentrations of 

 0.1-2 mg/cu m. [IARC. Monographs on the Evaluation of the Carcinogenic 

 Risk of Chemicals to Man. Geneva: World Health Organization, International 

 Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V52 

 441 (1991)] **PEER REVIEWED** 

 /HUMAN EXPOSURE STUDIES/ Many metal alloys contain cobalt together with 

 nickel. .../In/ 4721 subjects ... 5.7% were patch test positive to 

 cobalt. Simultaneous allergy to nickel and cobalt is frequent, and cobalt 

 has been considered of significance in persistent hand eczema in patients 

 with positive patch tests for nickel and cobalt. [Chang, L.W. (ed.). 

 Toxicology of Metals. Boca Raton, FL: Lewis Publishers, 1996, p. 829] 

 **PEER REVIEWED** 

 /SIGNS AND SYMPTOMS/ EFFECTS OF SHORT-TERM EXPOSURE: Inhalation of dust 

 may cause asthmatic reactions [IPCS, CEC; International Chemical Safety 

 Card on Cobalt. (October 1997). Available from, as of May 14, 2003: 

 http://www.inchem.org/documents/icsc/icsc/eics1128.htm ] **PEER REVIEWED** 

 

 /CASE REPORTS/ Four patients were found to react to occupational exposure 

 to grinding of hard metal (tungsten carbide). Three of the patients had 

 symptoms and signs compatible with an allergic alveolitis, the symptoms 

 disappearing and the chest radiograph clearing when they were absent from 

 work for a few months. Re-exposure to the offending agent led to new signs 

 and symptoms. The first patient was re-exposed twice and each time reacted 

 a little more seriously. After the last episode her chest radiograph has 

 not cleared completely, in contrast to the first two times. The fourth 

 patient had more typical occupational asthma. All the cases occurred in 

 the part of the factory where air concentrations of cobalt were the 

 lowest. The cobalt there is dissolved in the coolant necessary for 

 grinding the hard metal. It occurs mainly in the ionised form, which is 

 known to react with proteins and therefore presumably acts as a hapten. 

 [Sjogren I et al; Thorax. 35 (9): 653-9 (1980)] **PEER REVIEWED** 

 /CASE REPORTS/ The purpose of this report is to present a case of 

 hard-metal disease in which the symptoms and findings were minimal early 

 in the disease, but further exposure rapidly led to a fatal outcome. ... A 

 22-year-old nonsmoking white male, employed for over four years in 

 hard-metal tool grinding, started experiencing a dry cough and shortness 

 of breath during exercise. Preliminary investigations did not reveal any 

 cause for these symptoms, and the patient continued to work. Several 

 months later he developed clinically apparent alveolitis with recurrent 

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 pneumothorax. Pulmonary infiltrates in chest radiographs did not disappear 

 during corticosteroid treatment. Soon it was evident that the patient had 

 irreversible pulmonary failure, and a bilateral lung transplantation was 

 performed. No signs of rejection were seen in the resected lungs. The 

 patient died of pneumonia five months later, but no signs of hard-metal 

 disease were found in the transplanted lung. ... [Ruokonen EL et al; 

 Scand J Work Environ Health 22(1): 62-5 (1996)] **PEER REVIEWED** 

 /CASE REPORTS/ A case of giant cell interstitial pneumonitis caused by 

 exposure to cobalt dust which was not identified as the etiological agent 

 initially and hence led to progression of the disease. The patient 

 subsequently improved following cessation of exposure and treatment with 

 oral corticosteriods, thereby stressing the importance of occupational 

 history in all cases of interstitial pulmonary fibrosis. [Sundaram P et 

 al; Indian J Chest Dis Allied Sci43(1): 47-9 (2001)] **PEER REVIEWED** 

 /CASE REPORTS/ Allergy to cobalt in fragments of metal in a war injury was 

 held to be responsible for unilateral exophthalmos and paresis of eye 

 muscles on the basis of skin tests and observation that the condition 

 became worse on an occasion when a cobalt containing medication was 

 administered for anemia. [Grant, W.M. Toxicology of the Eye. 3rd ed. 

 Springfield, IL: Charles C. Thomas Publisher, 1986., p. 248] **PEER 

 REVIEWED** 

 /EPIDEMIOLOGY STUDIES/ The study population was comprised of 110 current 

 and former cobalt workers who had worked more than 10 years in a cobalt 

 plant. The reference group consisted of 140 unexposed workers. All the 

 participants were men. The analysis was based on exposure history, 

 pulmonary function, chest X-ray findings, and symptom questionnaires. 

 Symptoms of asthma based on questionnaire responses were statistically 

 more prevalent among the exposed workers. The respiratory flow rates 

 MEF(25) and MEF(50), which refer to smaller airways, were significantly 

 lower among the smoking exposed workers than among the smoking unexposed 

 workers. The causative factors of these symptoms and pulmonary function 

 changes could not be determined by the study. One new case of cobalt 

 asthma and one case of allergic asthma were diagnosed in the exposed 

 population. No cases of hard metal disease or fibrosing alveolitis were 

 found. [Linna A et al; Am J Ind Med 44(2): 124-32 (2003)] **PEER 

 REVIEWED** 

 /EPIDEMIOLOGY STUDIES/ The relationship between cobalt exposure and 

 respiratory disease was studied in a retrospective cohort of 319 workers 

 from a hard metal factory in Japan. The period of followup was 1981-1984. 

 Mean duration of exposure was 10.3 yr and mean airborne cobalt 

 concentrations ranged from 3-1292 ug/cu m. Eighteen workers had 

 occupational asthma related to exposure to hard metal, a prevalence rate 

 of 5.6%. Nine of the 18 had positive bronchial provocation tests with 

 cobalt and 2 of these 9 had positive patch tests to cobalt. The remaining 

 9 refused to be tested. [Kusaka Y et al; Br J Ind Med 43: 474-85 (1986)] 

 **PEER REVIEWED** 

 /BIOMONITORING/ In a cross sectional study, 38 production workers exposed 

 to nickel and 35 exposed to cobalt were examined for the content of nickel 

 and cobalt in hair, serum concentration levels of immunoglobulins, and 

 serum proteins. Age matched healthy males without exposure to nickel or 

 cobalt were selected as controls. No information was provided on dose or 

 duration of exposure. The respective geometric mean values of nickel and 

 cobalt in the hair of nickel exposed workers were 216.75 and 3.31 ug/g and 

 in cobalt exposed workers were 34.5 and 96.8 ug/g, respectively. These 

 values were significantly higher than respective control values (nickel: 

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 3.31 ug/g, cobalt: 0.38 ug/g). Tests for serum immunoglobulins revealed 

 that nickel workers differed from controls by exhibiting significantly 

 elevated IgG (p < 0.005), IgA (p < 0.01), and IgM (p < 0.005) levels 

 and that cobalt workers differed from controls by a significant elevation 

 of IgA level (p < 0.05). Both workers exposed to nickel or to cobalt 

 exhibited a significant drop in IgE level (0.001 < p < 0.05). There 

 was a significant elevation (p < 0.001, p < 0.005) in the 

 concentration of the serum proteins, alpha-antitrypsin, 

 alpha-two-macroglobulin, ceruloplasmin, and lysozyme, in exposed workers 

 when compared to controls. [Bencko V et al; Environ Res 40: 399-410 

 (1986)] **PEER REVIEWED** 

 /BIOMONITORING/ ...The authors report that /hard metal disease/ HMD is 

 strongly associated with residue Glu-69 of the /human leukocyte antigen/ 

 HLA-DP beta chain. All patients, except for one with a rare genotype, 

 possessed this marker as compared to 17 out of 35 exposed unaffected 

 individuals (p = 0.0014). These data allow us to genetically distinguish a 

 subgroup of cobalt-exposed individuals at risk for HMD, independently from 

 the more common allergic reaction. [Potolicchio I et al; Eur J Immunol 

 27(10): 2741-3 (1997)] **PEER REVIEWED** 

SKIN, EYE AND RESPIRATORY IRRITATIONS: 

 Cobalt dust is mildly irritating to the eyes and to a lesser extent to the 

 skin. /Cobalt dust/ [Sittig, M. Handbook of Toxic and Hazardous Chemicals 

 and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 

 1985., p. 254] **PEER REVIEWED** 

DRUG WARNINGS: 

 Of 212 patients undergoing total hip replacement who were tested 

 preoperatively for sensitivity to nickel, chromium, and cobalt, 14 showed 

 sensitivity. [DEUTMAN R ET AL; J BONE JT SURG AM 59 (7): 862-5 (1977)] 

 **PEER REVIEWED** 

 Manufactures of orthopedic fracture implants have turned to titanium in a 

 pure form and an alloy during the past ten to fifteen years. Although 

 primarily because of the biomechanical properties of this metal, concern 

 for allergy to nickel and chromium ions in stainless steel was a factor in 

 these decisions. ...To document the incidence of baseline sensitivity to 

 metal ions and the incidence of conversion to sensitivity to one of three 

 ions in stainless steel in a population of trauma patients ...patients 

 eighteen years of age and older with no history of metallic implants were 

 recruited ... between October 1995 and July 1997. Four hundred 

 ninety-three patients had a Finn chamber device with chromium, nickel, and 

 cobalt ions ... . Two hundred forty-two of these patients had placement of 

 a second patch, at a mean interval of 187 days (range 45 to 589 days). 

 /All received internal fixation of fracture or osteotomy with metal 

 implant. ... Prevalence of sensitivity to chromium was 0.2 percent, to 

 nickel 1.3 percent, and to cobalt 1.8 percent. Rates for conversion from a 

 negative to positive status were 2.7 percent for chromium, 3.8 percent for 

 nickel, and 3.8 percent for cobalt. Rates for desensitization (i.e., 

 converting from a positive to negative status) were 2.1 percent for nickel 

 and 3.8 percent for cobalt. Conclusion: The prevalence of sensitivity to 

 nickel, cobalt, and chromium is apparently low. Similarly, internal 

 fixation devices composed of stainless steel appear to result in an equal 

 incidence of conversion to metal ionic sensitivity and desensitization to 

 metal ions. It is conceivable that cutaneous sensitivity is not 

 representative of deep immune response. [Swiontkowski MF et al; J 

 Orthopaedic Trauma 15: 86-9 (2001)] **PEER REVIEWED** 

 Metal ion toxicity is a major cause for concern in metal-metal hip 

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 replacements. [Catelas I et al; Biomaterials 24(3): 383-91 (2003)] **PEER 

 REVIEWED** 

 ...The results obtained confirm the presence of an increase of cobalt in 

 the blood of patients after total hip replacement, while the chromium 

 levels are almost alike: average values in patients operated are 4.1+/-1.5 

 microg/L for cobalt (0.3 +/-0.1 microg/L in the control group) and 4.5 +/- 

 2.9 microg/L for chromium (4.7 +/- 2.4 microg/L in the control group). ... 

 [Adami G et al; Ann Chim. 93 (1-2): 1-10 (2003)] **PEER REVIEWED** 

 ...The cobalt and chromium concentrations in the serum and urine of 32 

 patients with current designed metal-on-metal total hip arthroplasty and 

 43 patients with conventional metal on ultrahigh molecular weight 

 polyethylene (UHMWPE) cementless total hip arthroplasty /were measured/. 

 ...Serum and urine chromium concentrations increased in 37.5% and 90.6%, 

 respectively, of 32 patients with well-fixed metal articulation (the mean 

 values were 0.09 ug/dL and 2.2 ug/L, respectively) and also increased in 

 28.6% and 85.7%, respectively, of 7 patients who received metal-on-UHMWPE 

 articulation with loosened acetabular component or stem made of Co/Cr 

 alloy (the mean values were 0.06 microg/dL and 1.6 ug/L, respectively). On 

 the other hand, the serum and urine cobalt concentrations were below the 

 detection limit in all patients. [Maezawa K et al; Arch Orthop Trauma 

 Surg 122 (5): 283-7 (2002)] **PEER REVIEWED** 

 ...In 259 patients who with total hip replacement, blood cobalt and 

 chromium concentrations were measured... over a period of four years after 

 arthroplasty. Of the patients enrolled in the study, 131 had been managed 

 with a METASUL cobalt-chromium alloy metal-on-metal bearing combination, 

 while 128 had been given a SIKOMET-SM21 cobalt-chromium alloy 

 metal-on-metal combination. The control group consisted of 31 age- and 

 gender-matched subjects. ...Compared with the controls, all the patients 

 had higher cobalt and chromium levels. Cobalt concentrations were up to 50 

 times higher, while chromium concentrations were up to 100 times higher. 

 ...Both systems showed evidence, in the whole-blood samples, of wear 

 debris production by the implants. Therefore, patients managed with 

 metal-on-metal bearing combinations should be carefully monitored in order 

 to ensure that any local or systemic complications are detected early on. 

 [Lhotka C et al; J Orthop Res 21 (2): 189-95 (2003)] **PEER REVIEWED** 

MEDICAL SURVEILLANCE: 

 The following medical procedures should be made available to each employee 

 who is exposed to cobalt metal fumes and dust at potentially hazardous 

 levels. Initial medical examination: A complete history and physical 

 examination: The purpose is to detect conditions that might place the 

 exposed employee at increased risk, and to establish a baseline for future 

 health monitoring. Examination of the respiratory system should be 

 stressed. The skin should be examined for evidence of chronic disorders. 

 14x17 inch chest roentgenogram: Cobalt may cause human lung damage. 

 Surveillance of the lungs is indicated. Forced Vital Capacity and Forced 

 Expiratory Volume (1 sec): Cobalt is reported to decrease pulmonary 

 function. Periodic surveillance is indicated. Periodic medical 

 examination: The aforementioned medical examinations should be repeated on 

 an annual basis. /Cobalt metal fume and dust/ [Mackison, F. W., R. S. 

 Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational 

 Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 

 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 

 1] **PEER REVIEWED** 

 In preemployment exam, special attention should be given to a history of 

 skin diseases, allergic dermatitis, baseline allergic resp diseases, and 

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 smoking history. ... Periodic exam should be directed toward skin and resp 

 symptoms and lung function. /Cobalt and cmpd/ [Sittig, M. Handbook of 

 Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, 

 NJ: Noyes Data Corporation, 1985., p. 254] **PEER REVIEWED** 

 The high-resolution computed tomography (HRCT) appearance of Hard metal 

 interstitial lung disease (HM-ILD) includes reticulation, traction 

 bronchiectasis, and large peripheral cystic spaces in a mid and upper lung 

 distribution. This appearance, along with a consistent occupational 

 exposure, should specifically suggest the diagnosis of HM-ILD. [Gotway MB 

 et al; J Thoracic Imaging 17 (4): 314-8 (2002)] **PEER REVIEWED** 

 Cobalt-exposed workers with inexplicable respiratory symptoms should be 

 closely monitored and the exposure should be suspended. [Ruokonen EL et 

 al; Scand J Work Environ Health 22(1): 62-5 (1996)] **PEER REVIEWED** 

POPULATIONS AT SPECIAL RISK: 

 /Protect/ ... from exposure those individuals with diseases of skin and 

 lung. [ITII. Toxic and Hazarous Industrial Chemicals Safety Manual. Tokyo, 

 Japan: The International Technical Information Institute, 1982., p. 134] 

 **PEER REVIEWED** 

 ...Workers with a history of skin diseases, allergic dermatitis, or 

 allergic respiratory disease. [Sittig, M. Handbook of Toxic and Hazardous 

 Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data 

 Corporation, 1985., p. 254] **PEER REVIEWED** 

 Metal dust inhalation induces an interstitial lung disease which may 

 progress to pulmonary fibrosis (hard metal disease, HMD). Cobalt is 

 believed to be the pathogenic agent of HMD. A strong genetic association 

 of HMD with some /human leukocyte antigen/ HLA-DP alleles has been 

 reported although the role of these molecules in the occurrence of the 

 fibrotic disorder remains unclear. A possible explanation of these 

 findings is that HLA-DP but not other HLA class II molecules can bind 

 cobalt... [Potolicchio I et al; Eur J Immunol 29(7): 2140-7 (1999)] 

 **PEER REVIEWED** 

 ...The recent finding that, in vitro, cobalt and metallic carbides 

 interact with oxygen to produce toxic activated oxygen species ... may 

 offer an alternative interpretation of the fact that only a limited 

 proportion of exposed workers develop interstitial disease. Besides the 

 possible involvement of immunological mechanisms, it may be speculated 

 that individuals with a lower antioxidant defense are more susceptible to 

 the toxic effect of activated oxygen species produced by cobalt-containing 

 dusts from hard metal. [Lison D et al; Eur Respir J 9 (5): 1024-8 (1996)] 

 **PEER REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 Cobalt concn in ambient air during use of hard metal /tungsten carbide 

 mixed with cobalt(2)/: range: 0.180-0.193 mg/cu m; personal sampling /From 

 table/(1). [(1) Seiler, H.G., H. Sigel and A. Sigel (eds.). Handbook on 

 the Toxicity of Inorganic Compounds. New York, NY: Marcel Dekker, Inc. p. 

 258 (1988) (2) CDC; MMWR Weekly. Jan 31, 1992. Pulmonary fibrosis 

 associated with occupational exposure to hard metal at a metal-coating 

 plant -- Connecticut, 1989. Available at 

 http://www.cdc.gov.mmwr/preview/mmwrhtnl/00016007.htm as of Jan 30, 2006.] 

 **PEER REVIEWED** 

 Cobalt concn in ambient air during grinding of hard metal: up to 61 ug/cu 

 m; stationary sampling /From table/ [Seiler, H.G., H. Sigel and A. Sigel 

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 (eds.). Handbook on the Toxicity of Inorganic Compounds. New York, NY: 

 Marcel Dekker, Inc. 1988., p. 259] **PEER REVIEWED** 

 Cobalt concn in ambient air during production of hard metal tools; mean 

 values between 28-367 ug/cu m; personal sampling /From table/ [Seiler, 

 H.G., H. Sigel and A. Sigel (eds.). Handbook on the Toxicity of Inorganic 

 Compounds. New York, NY: Marcel Dekker, Inc. 1988., p. 259] **PEER 

 REVIEWED** 

 Cobalt concn in ambient air during production of hard metal; breathable 

 dust range: 0.3-15 mg/cu m with 4-17% cobalt /From table/ [Seiler, H.G., 

 H. Sigel and A. Sigel (eds.). Handbook on the Toxicity of Inorganic 

 Compounds. New York, NY: Marcel Dekker, Inc. 1988., p. 259] **PEER 

 REVIEWED** 

 Cobalt concn in ambient air during production of hard metal; range: approx 

 0.002-0.1 mg/cu m; median value: approx 0.01 mg/cu m; personal sampling 

 /From table/ [Seiler, H.G., H. Sigel and A. Sigel (eds.). Handbook on the 

 Toxicity of Inorganic Compounds. New York, NY: Marcel Dekker, Inc. 1988., 

 p. 259] **PEER REVIEWED** 

 Inhalation is a potential route of exposure occurring most commonly when 

 material containing cobalt is heated, where cobalt powders are handled 

 manually, or where cobalt materials are subjected to grinding. Dermal 

 exposure to cobalt can occur in any operation where these materials are 

 handled manually, but it is a special consideration where solutions 

 containing cobalt are present. [NIOSH; Criteria Document: Cobalt p.1 

 (1981) DHEW Pub. NIOSH 82-107] **PEER REVIEWED** 

 ... COBALT ALLERGY IS SEEN IN MANY OCCUPATIONS INCL BUILDING & CIVIL 

 ENGINEERING METALWORK, PRINTING, AND POTTERY, LEATHER AND TEXTILE 

 INDUSTRIES; COBALT MAY SOMETIMES BE THE CAUSATIVE AGENT IN CEMENT ECZEMA. 

 /COBALT, ALLOYS & CMPD/ [International Labour Office. Encyclopedia of 

 Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: 

 International Labour Office, 1983., p. 495] **PEER REVIEWED** 

 ... SURVEY MADE BY THE PENNSYLVANIA DEPT OF HEALTH SHOWED BREATHING ZONE 

 CONCN COULD BE CONTROLLED TO ABOUT 0.07 MG/CU M /COBALT METAL FUME & 

 DUST/; WITHOUT CONTROL, CONCN WERE ABOUT 0.5 MG/CU M. [American Conference 

 of Governmental Industrial Hygienists. Documentation of the Threshold 

 Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: 

 American Conference of Governmental Industrial Hygienists, 1986., p. 144] 

 **PEER REVIEWED** 

 Occupations with potential exposure to cobalt: acetic acid makers; alloy 

 makers; alnico magnet makers; ammonia mask makers; barometer makers; 

 bright platers; catalyst workers; cement makers; cemented carbide workers; 

 ceramic workers; cement makers; cobalt soap makers; cosmetic makers; dye 

 workers; drug makers; electroplaters; enamelers; ethyl acrylate makers; 

 fertilizer workers; frit workers; gas mask makers; gasoline blenders; 

 glass colorers; glaze workers; high-speed tool steel workers; hygrometer 

 makers; ink makers; iron-cobalt platers; lamp filament makers; magnet 

 steel workers; metal smelterers; nickel by-product workers; paint drier 

 makers; painters; porcelain workers; protective-coating makers; refractory 

 brick makers; rubber makers; silicate paint makers; stone preserver 

 makers; weatherproof cement makers; welders. /From table/ /Cobalt and 

 cmpd/ [NIOSH; Criteria Document: Cobalt p.28 (1981) DHEW Pub. NIOSH 

 82-107] **PEER REVIEWED** 

 More than a million workers in the USA are potentially exposed to cobalt 

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 or its cmpd, many of them, however, to a limited degree, eg, when using 

 cobalt-containing paint driers. Heavier exposure may result from mining 

 processes, in the production of cobalt powder and alloys and in the 

 cemented tungsten carbide industry. /Cobalt & cmpd/ [Seiler, H.G., H. 

 Sigel and A. Sigel (eds.). Handbook on the Toxicity of Inorganic 

 Compounds. New York, NY: Marcel Dekker, Inc. 1988., p. 253] **PEER 

 REVIEWED** 

 Liberation during grinding and sharpening of cemented carbide and steel 

 tools; during synthesis of cobalt cmpd for use as catalysts and driers; 

 during refining and concn of ores. /Cobalt metal, fumes and dust/ 

 [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). 

 NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. 

 DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. 

 Government Printing Office, Jan. 1981., p. 3] **PEER REVIEWED** 

 Liberation during manufacture of metal items from cutting tool and tool 

 steels; during manufacture of metal items from hard facing alloys; during 

 manufacture of items containing low-expansion alloys; during manufacture 

 of metal items containing constant-modulus alloys; metal to glass seals in 

 electric lamps, vacuum tubes, and x-ray tubes. /Cobalt metal, fumes and 

 dust/ [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). 

 NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. 

 DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. 

 Government Printing Office, Jan. 1981., p. 3] **PEER REVIEWED** 

 Liberation during manufacture of dental prosthetic and osteosynthetic 

 items; during asbestos fiber processing. /Cobalt metal, fumes and dust/ 

 [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). 

 NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. 

 DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. 

 Government Printing Office, Jan. 1981., p. 3] **PEER REVIEWED** 

 The toxicologically important routes of entry for cobalt metal, fume, and 

 dust (as Co) are inhalation, ingestion, and skin and/or eye contact. 

 [NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases 

 CD-ROM. Department of Health & Human Services, Centers for Disease 

 Prevention & Control. National Institute for Occupational Safety & 

 Health. DHHS (NIOSH) Publication No. 2005-151 (2005)] **PEER REVIEWED** 

BODY BURDEN: 

 Type of exposure: producing cobalt powder; cobalt concn in blood: mean 

 values of 5-48 ug/L; in urine: mean values of 19-438 ug/L; sampling post 

 shift /From table/ [Seiler, H.G., H. Sigel and A. Sigel (eds.). Handbook 

 on the Toxicity of Inorganic Compounds. New York, NY: Marcel Dekker, Inc. 

 1988., p. 258] **PEER REVIEWED** 

 Type of exposure: grinding of hard metal; cobalt concn in serum: 2.1 ug/L; 

 in urine: 18.0 ug/L; /From table/ [Seiler, H.G., H. Sigel and A. Sigel 

 (eds.). Handbook on the Toxicity of Inorganic Compounds. New York, NY: 

 Marcel Dekker, Inc. 1988., p. 259] **PEER REVIEWED** 

 Type of exposure: producing hard metal tools; cobalt concn in blood: mean 

 value between 3.3-18.7 ug/L; in urine: between 10-235 ug/L; sampling at 

 Wednesday or Tuesday shift end /From table/ [Seiler, H.G., H. Sigel and A. 

 Sigel (eds.). Handbook on the Toxicity of Inorganic Compounds. New York, 

 NY: Marcel Dekker, Inc. 1988., p. 259] **PEER REVIEWED** 

 Type of exposure: producing hard metal; cobalt concn in blood: mean value 

 between 2.0 and 18.3 ug.l; in urine: between 64. and 64.3 ug/g creatinine; 

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 /From table/ [Seiler, H.G., H. Sigel and A. Sigel (eds.). Handbook on the 

 Toxicity of Inorganic Compounds. New York, NY: Marcel Dekker, Inc. 1988., 

 p. 259] **PEER REVIEWED** 

EVIDENCE FOR CARCINOGENICITY: 

 A3: Confirmed animal carcinogen with unknown relevance to humans. /Cobalt 

 and inorganic compounds, as Co/ [American Conference of Governmental 

 Industrial Hygienists TLVs and BEIs. Threshold Limit Values for Chemical 

 Substances and Physical Agents and Biological Exposure Indices. 

 Cincinnati, OH, 2008, p. 21] **QC REVIEWED** 

DRUG WARNINGS: 

 Of 212 patients undergoing total hip replacement who were tested 

 preoperatively for sensitivity to nickel, chromium, and cobalt, 14 showed 

 sensitivity. [DEUTMAN R ET AL; J BONE JT SURG AM 59 (7): 862-5 (1977)] 

 **PEER REVIEWED** 

 Manufactures of orthopedic fracture implants have turned to titanium in a 

 pure form and an alloy during the past ten to fifteen years. Although 

 primarily because of the biomechanical properties of this metal, concern 

 for allergy to nickel and chromium ions in stainless steel was a factor in 

 these decisions. ...To document the incidence of baseline sensitivity to 

 metal ions and the incidence of conversion to sensitivity to one of three 

 ions in stainless steel in a population of trauma patients ...patients 

 eighteen years of age and older with no history of metallic implants were 

 recruited ... between October 1995 and July 1997. Four hundred 

 ninety-three patients had a Finn chamber device with chromium, nickel, and 

 cobalt ions ... . Two hundred forty-two of these patients had placement of 

 a second patch, at a mean interval of 187 days (range 45 to 589 days). 

 /All received internal fixation of fracture or osteotomy with metal 

 implant. ... Prevalence of sensitivity to chromium was 0.2 percent, to 

 nickel 1.3 percent, and to cobalt 1.8 percent. Rates for conversion from a 

 negative to positive status were 2.7 percent for chromium, 3.8 percent for 

 nickel, and 3.8 percent for cobalt. Rates for desensitization (i.e., 

 converting from a positive to negative status) were 2.1 percent for nickel 

 and 3.8 percent for cobalt. Conclusion: The prevalence of sensitivity to 

 nickel, cobalt, and chromium is apparently low. Similarly, internal 

 fixation devices composed of stainless steel appear to result in an equal 

 incidence of conversion to metal ionic sensitivity and desensitization to 

 metal ions. It is conceivable that cutaneous sensitivity is not 

 representative of deep immune response. [Swiontkowski MF et al; J 

 Orthopaedic Trauma 15: 86-9 (2001)] **PEER REVIEWED** 

 Metal ion toxicity is a major cause for concern in metal-metal hip 

 replacements. [Catelas I et al; Biomaterials 24(3): 383-91 (2003)] **PEER 

 REVIEWED** 

 ...The results obtained confirm the presence of an increase of cobalt in 

 the blood of patients after total hip replacement, while the chromium 

 levels are almost alike: average values in patients operated are 4.1+/-1.5 

 microg/L for cobalt (0.3 +/-0.1 microg/L in the control group) and 4.5 +/- 

 2.9 microg/L for chromium (4.7 +/- 2.4 microg/L in the control group). ... 

 [Adami G et al; Ann Chim. 93 (1-2): 1-10 (2003)] **PEER REVIEWED** 

 ...The cobalt and chromium concentrations in the serum and urine of 32 

 patients with current designed metal-on-metal total hip arthroplasty and 

 43 patients with conventional metal on ultrahigh molecular weight 

 polyethylene (UHMWPE) cementless total hip arthroplasty /were measured/. 

 ...Serum and urine chromium concentrations increased in 37.5% and 90.6%, 

 respectively, of 32 patients with well-fixed metal articulation (the mean 

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 values were 0.09 ug/dL and 2.2 ug/L, respectively) and also increased in 

 28.6% and 85.7%, respectively, of 7 patients who received metal-on-UHMWPE 

 articulation with loosened acetabular component or stem made of Co/Cr 

 alloy (the mean values were 0.06 microg/dL and 1.6 ug/L, respectively). On 

 the other hand, the serum and urine cobalt concentrations were below the 

 detection limit in all patients. [Maezawa K et al; Arch Orthop Trauma 

 Surg 122 (5): 283-7 (2002)] **PEER REVIEWED** 

 ...In 259 patients who with total hip replacement, blood cobalt and 

 chromium concentrations were measured... over a period of four years after 

 arthroplasty. Of the patients enrolled in the study, 131 had been managed 

 with a METASUL cobalt-chromium alloy metal-on-metal bearing combination, 

 while 128 had been given a SIKOMET-SM21 cobalt-chromium alloy 

 metal-on-metal combination. The control group consisted of 31 age- and 

 gender-matched subjects. ...Compared with the controls, all the patients 

 had higher cobalt and chromium levels. Cobalt concentrations were up to 50 

 times higher, while chromium concentrations were up to 100 times higher. 

 ...Both systems showed evidence, in the whole-blood samples, of wear 

 debris production by the implants. Therefore, patients managed with 

 metal-on-metal bearing combinations should be carefully monitored in order 

 to ensure that any local or systemic complications are detected early on. 

 [Lhotka C et al; J Orthop Res 21 (2): 189-95 (2003)] **PEER REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 Cobalt concn in ambient air during use of hard metal /tungsten carbide 

 mixed with cobalt(2)/: range: 0.180-0.193 mg/cu m; personal sampling /From 

 table/(1). [(1) Seiler, H.G., H. Sigel and A. Sigel (eds.). Handbook on 

 the Toxicity of Inorganic Compounds. New York, NY: Marcel Dekker, Inc. p. 

 258 (1988) (2) CDC; MMWR Weekly. Jan 31, 1992. Pulmonary fibrosis 

 associated with occupational exposure to hard metal at a metal-coating 

 plant -- Connecticut, 1989. Available at 

 http://www.cdc.gov.mmwr/preview/mmwrhtnl/00016007.htm as of Jan 30, 2006.] 

 **PEER REVIEWED** 

 Cobalt concn in ambient air during grinding of hard metal: up to 61 ug/cu 

 m; stationary sampling /From table/ [Seiler, H.G., H. Sigel and A. Sigel 

 (eds.). Handbook on the Toxicity of Inorganic Compounds. New York, NY: 

 Marcel Dekker, Inc. 1988., p. 259] **PEER REVIEWED** 

 Cobalt concn in ambient air during production of hard metal tools; mean 

 values between 28-367 ug/cu m; personal sampling /From table/ [Seiler, 

 H.G., H. Sigel and A. Sigel (eds.). Handbook on the Toxicity of Inorganic 

 Compounds. New York, NY: Marcel Dekker, Inc. 1988., p. 259] **PEER 

 REVIEWED** 

 Cobalt concn in ambient air during production of hard metal; breathable 

 dust range: 0.3-15 mg/cu m with 4-17% cobalt /From table/ [Seiler, H.G., 

 H. Sigel and A. Sigel (eds.). Handbook on the Toxicity of Inorganic 

 Compounds. New York, NY: Marcel Dekker, Inc. 1988., p. 259] **PEER 

 REVIEWED** 

 Cobalt concn in ambient air during production of hard metal; range: approx 

 0.002-0.1 mg/cu m; median value: approx 0.01 mg/cu m; personal sampling 

 /From table/ [Seiler, H.G., H. Sigel and A. Sigel (eds.). Handbook on the 

 Toxicity of Inorganic Compounds. New York, NY: Marcel Dekker, Inc. 1988., 

 p. 259] **PEER REVIEWED** 

 Inhalation is a potential route of exposure occurring most commonly when 

 material containing cobalt is heated, where cobalt powders are handled 

 manually, or where cobalt materials are subjected to grinding. Dermal 

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 exposure to cobalt can occur in any operation where these materials are 

 handled manually, but it is a special consideration where solutions 

 containing cobalt are present. [NIOSH; Criteria Document: Cobalt p.1 

 (1981) DHEW Pub. NIOSH 82-107] **PEER REVIEWED** 

 ... COBALT ALLERGY IS SEEN IN MANY OCCUPATIONS INCL BUILDING & CIVIL 

 ENGINEERING METALWORK, PRINTING, AND POTTERY, LEATHER AND TEXTILE 

 INDUSTRIES; COBALT MAY SOMETIMES BE THE CAUSATIVE AGENT IN CEMENT ECZEMA. 

 /COBALT, ALLOYS & CMPD/ [International Labour Office. Encyclopedia of 

 Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: 

 International Labour Office, 1983., p. 495] **PEER REVIEWED** 

 ... SURVEY MADE BY THE PENNSYLVANIA DEPT OF HEALTH SHOWED BREATHING ZONE 

 CONCN COULD BE CONTROLLED TO ABOUT 0.07 MG/CU M /COBALT METAL FUME & 

 DUST/; WITHOUT CONTROL, CONCN WERE ABOUT 0.5 MG/CU M. [American Conference 

 of Governmental Industrial Hygienists. Documentation of the Threshold 

 Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: 

 American Conference of Governmental Industrial Hygienists, 1986., p. 144] 

 **PEER REVIEWED** 

 Occupations with potential exposure to cobalt: acetic acid makers; alloy 

 makers; alnico magnet makers; ammonia mask makers; barometer makers; 

 bright platers; catalyst workers; cement makers; cemented carbide workers; 

 ceramic workers; cement makers; cobalt soap makers; cosmetic makers; dye 

 workers; drug makers; electroplaters; enamelers; ethyl acrylate makers; 

 fertilizer workers; frit workers; gas mask makers; gasoline blenders; 

 glass colorers; glaze workers; high-speed tool steel workers; hygrometer 

 makers; ink makers; iron-cobalt platers; lamp filament makers; magnet 

 steel workers; metal smelterers; nickel by-product workers; paint drier 

 makers; painters; porcelain workers; protective-coating makers; refractory 

 brick makers; rubber makers; silicate paint makers; stone preserver 

 makers; weatherproof cement makers; welders. /From table/ /Cobalt and 

 cmpd/ [NIOSH; Criteria Document: Cobalt p.28 (1981) DHEW Pub. NIOSH 

 82-107] **PEER REVIEWED** 

 More than a million workers in the USA are potentially exposed to cobalt 

 or its cmpd, many of them, however, to a limited degree, eg, when using 

 cobalt-containing paint driers. Heavier exposure may result from mining 

 processes, in the production of cobalt powder and alloys and in the 

 cemented tungsten carbide industry. /Cobalt & cmpd/ [Seiler, H.G., H. 

 Sigel and A. Sigel (eds.). Handbook on the Toxicity of Inorganic 

 Compounds. New York, NY: Marcel Dekker, Inc. 1988., p. 253] **PEER 

 REVIEWED** 

 Liberation during grinding and sharpening of cemented carbide and steel 

 tools; during synthesis of cobalt cmpd for use as catalysts and driers; 

 during refining and concn of ores. /Cobalt metal, fumes and dust/ 

 [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). 

 NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. 

 DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. 

 Government Printing Office, Jan. 1981., p. 3] **PEER REVIEWED** 

 Liberation during manufacture of metal items from cutting tool and tool 

 steels; during manufacture of metal items from hard facing alloys; during 

 manufacture of items containing low-expansion alloys; during manufacture 

 of metal items containing constant-modulus alloys; metal to glass seals in 

 electric lamps, vacuum tubes, and x-ray tubes. /Cobalt metal, fumes and 

 dust/ [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). 

 NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. 

 DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. 

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 Government Printing Office, Jan. 1981., p. 3] **PEER REVIEWED** 

 Liberation during manufacture of dental prosthetic and osteosynthetic 

 items; during asbestos fiber processing. /Cobalt metal, fumes and dust/ 

 [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). 

 NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. 

 DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. 

 Government Printing Office, Jan. 1981., p. 3] **PEER REVIEWED** 

 The toxicologically important routes of entry for cobalt metal, fume, and 

 dust (as Co) are inhalation, ingestion, and skin and/or eye contact. 

 [NIOSH. NIOSH Pocket Guide to Chemical Hazards & Other Databases 

 CD-ROM. Department of Health & Human Services, Centers for Disease 

 Prevention & Control. National Institute for Occupational Safety & 

 Health. DHHS (NIOSH) Publication No. 2005-151 (2005)] **PEER REVIEWED** 

BODY BURDEN: 

 Type of exposure: producing cobalt powder; cobalt concn in blood: mean 

 values of 5-48 ug/L; in urine: mean values of 19-438 ug/L; sampling post 

 shift /From table/ [Seiler, H.G., H. Sigel and A. Sigel (eds.). Handbook 

 on the Toxicity of Inorganic Compounds. New York, NY: Marcel Dekker, Inc. 

 1988., p. 258] **PEER REVIEWED** 

 Type of exposure: grinding of hard metal; cobalt concn in serum: 2.1 ug/L; 

 in urine: 18.0 ug/L; /From table/ [Seiler, H.G., H. Sigel and A. Sigel 

 (eds.). Handbook on the Toxicity of Inorganic Compounds. New York, NY: 

 Marcel Dekker, Inc. 1988., p. 259] **PEER REVIEWED** 

 Type of exposure: producing hard metal tools; cobalt concn in blood: mean 

 value between 3.3-18.7 ug/L; in urine: between 10-235 ug/L; sampling at 

 Wednesday or Tuesday shift end /From table/ [Seiler, H.G., H. Sigel and A. 

 Sigel (eds.). Handbook on the Toxicity of Inorganic Compounds. New York, 

 NY: Marcel Dekker, Inc. 1988., p. 259] **PEER REVIEWED** 

 Type of exposure: producing hard metal; cobalt concn in blood: mean value 

 between 2.0 and 18.3 ug.l; in urine: between 64. and 64.3 ug/g creatinine; 

 /From table/ [Seiler, H.G., H. Sigel and A. Sigel (eds.). Handbook on the 

 Toxicity of Inorganic Compounds. New York, NY: Marcel Dekker, Inc. 1988., 

 p. 259] **PEER REVIEWED** 

SKIN, EYE AND RESPIRATORY IRRITATIONS: 

 Cobalt dust is mildly irritating to the eyes and to a lesser extent to the 

 skin. /Cobalt dust/ [Sittig, M. Handbook of Toxic and Hazardous Chemicals 

 and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 

 1985., p. 254] **PEER REVIEWED** 

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The following information was generated from the 

Hazardous Substances Data Bank (HSDB), 

a database of the National Library of Medicine's TOXNET system 

(http://toxnet.nlm.nih.gov) on October 27, 2009. 

Query: The chemical name copper was identified. 

The following terms were added from ChemIDplus: 

bronze powder 

raney copper 

ofhc cu 

kafar copper 

gold bronze 

copper bronze 

arwood copper 

copper powder 

CAS Registry Number: 7440-50-8 

1 

NAME: COPPER, ELEMENTAL 

RN: 7440-50-8 

NOTE: 

 This record contains information for copper in its zero valence state 

 only. For general toxicity and environmental fate of copper and copper 

 compounds, refer to the COPPER COMPOUNDS record; for compound-specific 

 information, to the appropriate individual record, e.g., cuprous iodide, 

 cupric sulfide, etc. 

HUMAN HEALTH EFFECTS: 

EVIDENCE FOR CARCINOGENICITY: 

 CLASSIFICATION: D; not classifiable as to human carcinogenicity. BASIS FOR 

 CLASSIFICATION: There are no human data, inadequate animal data from 

 assays of copper compounds, and equivocal mutagenicity data. HUMAN 

 CARCINOGENICITY DATA: None. ANIMAL CARCINOGENICITY DATA: Inadequate. [U.S. 

 Environmental Protection Agency's Integrated Risk Information System 

 (IRIS) on Copper (7440-50-8) Available from: 

 http://www.epa.gov/ngispgm3/iris on the Substance File List as of March 

 15, 2000] **PEER REVIEWED** 

HUMAN TOXICITY EXCERPTS: 

 COPPER ITSELF PROBABLY HAS LITTLE OR NO TOXICITY, ALTHOUGH THERE ARE 

 CONFLICTING REPORTS IN LITERATURE. [The Merck Index. 10th ed. Rahway, New 

 Jersey: Merck Co., Inc., 1983., p. 359] **PEER REVIEWED** 

 The fumes and dust cause irritation of the upper respiratory tract. 

 [Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 

 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985., p. 257] 

 **PEER REVIEWED** 

 Inhalation of dusts & fumes of metallic copper ... causes congestion 

 of nasal mucous membranes, ulceration & perforation of the nasal 

 septum, & pharyngeal congestion. [Venugopal, B. and T.D. Luckey. Metal 

 Toxicity in Mammals, 2. New York: Plenum Press, 1978., p. 27] **PEER 

 REVIEWED** 

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 Fumes from the heating of metallic copper can cause metal fume fever, 

 nausea, gastric pain, & diarrhea. [International Labour Office. 

 Encyclopaedia of Occupational Health and Safety. 4th edition, Volumes 1-4 

 1998. Geneva, Switzerland: International Labour Office, 1998., p. 63.14] 

 **PEER REVIEWED** 

 Acute poisoning from inhalation of copper containing dust has ... been 

 reported ... to cause symptoms of heavy metal poisoning ... . [Browning, 

 E. Toxicity of Industrial Metals. 2nd ed. New York: 

 Appleton-Century-Crofts, 1969., p. 149] **PEER REVIEWED** 

 ... Symptoms of acute gastrointestinal disturbance /pain in chest, 

 metallic taste in mouth, nausea, vomiting/, as well as some respiratory 

 irritation & dyspnea were observed ... /in an/ extensive investigation 

 /about 1,910/ of workers exposed to the dust of metallic copper & its 

 oxides, but ... the digestive disturbance /was attributed/ to the 

 conversion of the swallowed metallic copper to its irritating salts, & 

 the respiratory symptoms to the non-specific reaction to the inhaled dust 

 as a foreign body in the lung. [Browning, E. Toxicity of Industrial 

 Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 149] **PEER 

 REVIEWED** 

 There is a report of corneal ulcers, & skin irritation, but little 

 other toxicity, in a copper-mine worker who fell into an electrolytic 

 bath, but the acidity, rather than the copper, may have been the cause. 

 [International Labour Office. Encyclopaedia of Occupational Health and 

 Safety. 4th edition, Volumes 1-4 1998. Geneva, Switzerland: International 

 Labour Office, 1998., p. 63.14] **PEER REVIEWED** 

 A report /is given/ of 2 children who developed green hair. Copper 

 absorbed from swimming pools was considered to be responsible, the source 

 being either copper piping or a copper-containing algicide. [Reynolds, 

 J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. 

 London: The Pharmaceutical Press, 1982., p. 930] **PEER REVIEWED** 

 IT IS DEBATABLE WHETHER CHRONIC COPPER POISONING, INDUSTRIAL OR 

 NONINDUSTRIAL, EXISTS IN HUMAN BEINGS. MANY CASES OF ILLNESS FORMERLY 

 ATTRIBUTED TO COPPER ARE NOW BELIEVED TO HAVE BEEN MORE PROBABLY DUE TO 

 ADMIXTURE WITH OTHER METALS, ESPECIALLY LEAD. [Browning, E. Toxicity of 

 Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 

 147] **PEER REVIEWED** 

 Chronic copper poisoning has been the subject of considerable dispute 

 since the middle of the 19th century, when the green coloration of the 

 skin of copper workers was thought by some authorities ... to be evidence 

 of injury to their health. This discoloration of skin, hair, & teeth 

 often seen in copper workers is not apparently assoc with ill health. ... 

 /A/ survey /reported in 1900/ of workers employed in the extraction of 

 metallic copper & the manufacture of bronze, some having been in this 

 employment for periods of ... 40 years ... concluded that, in these 

 workers at least, there was no evidence in favor of chronic copper 

 poisoning as an entity. [Browning, E. Toxicity of Industrial Metals. 2nd 

 ed. New York: Appleton-Century-Crofts, 1969., p. 149] **PEER REVIEWED** 

 ... More recent observers /than in 1900/ have reported various 

 disturbances of health particularly related to the nervous system, which 

 they attribute to chronic exposure to copper & its compounds, but none 

 is prepared to make any more definite statement than that the cause of the 

 symptoms was "probably" chronic copper poisoning. Such were the cases of 4 

 brass founders ... /reported in 1932/ who complained of giddiness, loss of 

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 appetite, excessive perspiration, & drowsiness; also that of a girl 

 ... /reported in 1931/ who developed Raynaud's disease after fragments of 

 copper had become embedded in her hand, the suggestion being that this 

 might be due to an affinity of copper for the sympathetic system ... . On 

 the evidence avail there does not appear to be any conclusive proof that 

 there exists a form of chronic copper poisoning affecting the central or 

 peripheral nervous system. [Browning, E. Toxicity of Industrial Metals. 

 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 149] **PEER 

 REVIEWED** 

 SINCE THE VAPORIZATION POINT OF COPPER IS HIGH, ABOUT 2,350 DEG C, IT IS 

 VERY RARE THAT FUMES OF THIS SORT /COPPER OXIDE/ ARE ENCOUNTERED IN 

 INDUSTRY. WORKMEN OFTEN SPEAK OF COPPER POISONING AS THEY DO OF BRASS 

 POISONING WHEN THEY MEAN INFECTED CUTS RESULTING FROM HANDLING OF SHARP 

 EDGED COPPER PLATES OR FRAGMENTS. IT IS IMPROBABLE THAT COPPER HAS ANY 

 CHEM ACTION IN SUCH CASES, WITH THE METAL ACTING AS FOREIGN BODY ONLY. 

 [Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, 

 Mass.: Publishing Sciences Group, Inc., 1974., p. 79] **PEER REVIEWED** 

 Copper & its alloys are usually driven into the eye by an explosion. 

 ... In the worst cases seen clinically the copper particle penetrates the 

 vitreous body to the retina. This is accompanied by hemorrhage, & 

 rapid formation of an abscess, soon followed by some degree of 

 encapsulation by connective tissue. The vitreous body characteristically 

 is disorganized & destroyed. Total retina detachment & phthisis 

 bulbi follow. In these circumstances there is no time for copper to 

 migrate forward & cause the discoloration of lens, cornea, & iris 

 as is seen in chronic chalcosis associated with less serious injuries. 

 Encapsulation of the foreign body may prolong the process in some cases, 

 but copper has tendency eventually to escape its encapsulation & to 

 continue to do damage. [Grant, W.M. Toxicology of the Eye. 3rd ed. 

 Springfield, IL: Charles C. Thomas Publisher, 1986., p. 261] **PEER 

 REVIEWED** 

 ... WHEN LENS HAS BEEN DIRECTLY ENTERED OR INJURED BY COPPER CONTAINING 

 FOREIGN BODY, THERE MAY BE FORMATION OF DENSE CATARACT & ACCOMPANYING 

 YELLOW GREEN DISCOLORATION OF LENS. [Grant, W. M. Toxicology of the Eye. 

 2nd ed. Springfield, Illinois: Charles C. Thomas, 1974., p. 313] **PEER 

 REVIEWED** 

 The intraocular pressure in eyes with copper foreign bodies is most often 

 not mentioned, but experienced observers have pointed out that when there 

 is a strong ocular reaction to copper in humans ... the pressure is 

 characteristically low. This may be due to reduction of aqueous formation. 

 ... In rare instances open angle glaucoma has developed in eyes with 

 disseminated chalcosis from copper foreign bodies, but not in endogenous 

 chalcosis of Wilson's disease. [Grant, W.M. Toxicology of the Eye. 3rd ed. 

 Springfield, IL: Charles C. Thomas Publisher, 1986., p. 264] **PEER 

 REVIEWED** 

 Verdigris, formed by atmospheric corrosion of the surface of metallic 

 copper presumably composed of copper carbonates & oxides, causes 

 immediate irritation & conjunctival inflammation when accidentally 

 dropped or dusted on the eyes of patients, but the reaction subsides 

 without permanent damage soon after the eye is cleaned by irrigation. 

 [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. 

 Thomas Publisher, 1986., p. 260] **PEER REVIEWED** 

 WELDERS EXPOSED TO COPPER FUMES ... /COMPLAINED OF SNEEZING, COUGHING, 

 DIGESTIVE DISORDERS, AND FEVER/. ... CHANGES IN NASAL MUCOSA OCCURRED, 

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 CONSISTING OF ATROPHIC RHINITIS WITH COMPLAINTS OF METALLIC TASTE, RUNNY 

 NOSE, AND MUCOSAL IRRITATION IN THE MOUTH AND EYES. ... NASAL ULCERATIONS 

 AND BLEEDING OCCURRED IN WORKERS INHALING FINELY DIVIDED COPPER METAL DUST 

 ... . ALLERGIC CONTACT DERMATITIS IS LESS COMMONLY ENCOUNTERED ... . 

 [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and 

 Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley 

 Sons, 1981-1982., p. 1628] **PEER REVIEWED** 

 Although copper itself has been known to cause keratinization of the palms 

 /of hands/ & soles /of feet/ it has not been widely recognized as a 

 frequent industrial cause of dermatitis. It is ... of interest to note ... 

 /a/ discription ... of 5 cases of dermatitis /reported in 1952/ in workers 

 in contact with brass, an alloy containing 2 parts of copper & 1 of 

 zinc, with trace amounts of other metals. In all ... cases, patch tests 

 were positive with brass & copper, & ... /it was/ believed that 

 the copper constituent (70%) was responsible. [Browning, E. Toxicity of 

 Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 

 150] **PEER REVIEWED** 

 Incubation of human spermatozoa with metallic copper is found to bring 

 about a significant fall in the percentage of motile sperm. [Friberg, L., 

 Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the 

 Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science 

 Publishers B.V., 1986., p. V2 247] **PEER REVIEWED** 

 A ONE YEAR FOLLOW UP STUDY IN HEALTHY WOMEN WAS UNDERTAKEN TO STUDY SERUM 

 FERRITIN AS WELL AS OTHER HEMATOLOGIC PARAMETERS PRIOR TO, & 6 & 

 12 MONTHS AFTER INSERTION OF AN INTRAUTERINE DEVICE, T COPPER 220. A 

 DIRECT RELATION BETWEEN LOW FERRITIN SERUM VALUES & ANEMIA DEVELOPMENT 

 WAS FOUND. MEASUREMENT OF SERUM FERRITIN LEVELS COULD BE A USEFUL TOOL TO 

 ANTICIPATE ANEMIA DEVELOPMENT IN WOMEN WITH INTRAUTERINE DEVICES. [PIEDRAS 

 J ET AL; CONTRACEPTION 27 (3): 289-97 (1983)] **PEER REVIEWED** 

 ANEMIA OCCURRED IN MEN OCCUPATIONALLY EXPOSED TO LOW LEVELS OF COPPER. 

 [FINELLI VN ET AL; HEAVY MET ENVIRON INT CONF 3RD: 475-8 (1981)] **PEER 

 REVIEWED** 

 IT IS GENERALLY AGREED THAT COPPER ITSELF IS LESS TOXIC THAN ITS SALTS ... 

 . [Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: 

 Appleton-Century-Crofts, 1969., p. 147] **PEER REVIEWED** 

 Several reports of acute hemolytic anemia in patients undergoing 

 hemodialysis have been attributed to excess copper in the dialysis fluid. 

 Leaching of copper from copper tubing in home units and from copper 

 filters and tubing within units have both been reported. Incr copper concn 

 are associated with soft water and acidic water. This effect has been 

 observed at copper concn from 22-50 ug/l in the dialysate. The problem can 

 be controlled by removing copper from the system and monitoring the pH and 

 conductivity of the dialysate. [USEPA; Drinking Water Criteria Document 

 for Copper (Final Draft) p.VI-14 (1985) EPA-600/X-84-190-1] **PEER 

 REVIEWED** 

 The contributions of sulfur dioxide and arsenic to lung cancer were 

 assessed in copper smelter workers with regard to the confounding variable 

 of cigarette smoking. The study included a total of 6,078 white male 

 workers who had worked for at least 3 years in a United States copper 

 smelter between the dates January 1, 1946, and December 31, 1976. Worker 

 exposure to arsenic, sulfur dioxide, dust, nickel, lead, and cadmium was 

 categorized by job and year. The mortality rates for lung cancer in United 

 States copper smelter workers are not unusually high except in one smelter 

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 that has a feed with a high arsenic content. [Enterline PE et al; J Occup 

 Med 29 (10): 831-38 (1987)] **PEER REVIEWED** 

 Concentrations of 11 metals (cadmium, lead, copper, iron, manganese, 

 cobalt, chromium, nickel, zinc, magnesium, and calcium) and protein in 

 human pancreatic juice were studied. Assuming the flow rate of pancreatic 

 juice to be 1500-2000 ml/day, the daily excretions of metals into duodenum 

 via pancreatic juice were calculated as follows (umoles of metal/day): 

 copper, 6.20-8.26; Toxic (cadmium and lead) and essential metals (copper, 

 zinc, iron, manganese, chromium, and nickel) are excreted daily into 

 duodenum via pancreatic juice. [Ishihara N et al; Arch Environ Health 42 

 (6): 356-60 (1987)] **PEER REVIEWED** 

 In a cross-sectional study of 20 gun-metal foundry workers (mean age 47 

 yr) the subclinical neurophysiological effects of exposure to lead, zinc, 

 copper, and tin were evaluated by "short-latency" somatosensory evoked 

 potential. Controls were age and height-matched males without occupational 

 exposure to lead. Range of employment was 1-16 yr (mean 10 yr). In exposed 

 workers mean blood lead was 42 ug/dl, mean zinc plasma 95 ug/dl, mean 

 copper plasma 105 ug/dl, and mean urinary tin 28 ug/l. In workers, the 

 interpeak latency in the cervico-spino-bulbar region (N9(Erb)-N13 latency) 

 was significantly prolonged, and the MCV and SCV in the forearm were 

 significantly slowed when compared with controls. MCV and SCV in the palm 

 were positively related to erythrocyte zinc concentration and plasma 

 copper concentration, respectively. [Araki S et al; Am J Ind Med 10:163-75 

 (1986)] **PEER REVIEWED** 

 Metal fume fever occurred among workers involved in cutting brass pipes 

 with electric torches in an enclosed, poorly ventilated steam condenser. 

 Symptoms most commonly reported among the 26 workers were fever (21), 

 dyspnea (23), chills (21), headache (21), and nausea (19). Fourteen of the 

 workers experienced the symptom of an unusual sweet or metallic taste in 

 the mouth. Clinical signs were limited to wheezing or rales in eight 

 patients; leukocytosis (21) and an elevation of band cell forms (20) were 

 seen in a total of 24 workers. The average time between exposure and onset 

 of symptoms was 5 hr. None of three workers who spent less than 1 hr in 

 the condenser became ill, whereas 25 of the 26 who spent more than 1 hr 

 became ill. Five of 12 workers had urine copper levels in excess of 0.05 

 mg/l [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and 

 Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, 

 NY: John Wiley & Sons Inc., 1993-1994., p. 2004] **PEER REVIEWED** 

 ... Exposure to copper dust at 0. 1 mg/cu m causes nausea and metal fume 

 fever, with reversible flu like symptoms. Metal fume fever (also called 

 brass founder's ague) is a transient condition and is characterized by 

 fever, chills, muscle pain, and vomiting. Recovery normally occurs within 

 24 to 48 hr. Tolerance may develop, but is generally lost over the 

 weekend. [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene 

 and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New 

 York, NY: John Wiley & Sons Inc., 1993-1994., p. 2004] **PEER 

 REVIEWED** 

 A form of contact dermatitis assoc with copper has been reported, but few 

 cases of dermatitis caused by copper ... or compounds occur in industry. 

 Copper allergies have been reported, either related to skin contact with 

 copper ... salts or to copper containing intrauterine devices. /Soluble 

 copper salts/ [Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. 

 (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: 

 Amsterdam: Elsevier Science Publishers B.V., 1986., p. V2 244] **PEER 

 REVIEWED** 

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 The chief effect from industrial exposures is on the upper resp tract, 

 expressing itself as a metal fume fever with atrophic changes in the nasal 

 mucous membranes & subjective effects associated with the irritative 

 nature of the copper fume, dusts, & mists. Sources of exposure are 

 from fume, from copper ore smelting & related metallurgic operations, 

 from welding, & from dusts of copper metal & copper salts in 

 copper metalworkers & copper polishers. /Copper fume, dusts, and 

 mists/ [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial 

 Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: 

 John Wiley Sons, 1981-1982., p. 1628] **PEER REVIEWED** 

 The acute inhalation of copper fume during refining or welding processes 

 may cause typical metal fume fever with upper respiratory irritation, 

 chills, and aching muscles. A number of workers who developed copper fume 

 fever had serum copper levels which averaged 1.26 mg/l. /Copper fume/ 

 [Cohen SR; J Occ Med 16: 621-4 (1974) as cited in Basett RC; Biological 

 Monitoring Methods for Industrial Chemicals p.88-9 (1980)] **PEER 

 REVIEWED** 

 The bronze powder, used for gilding Christmas cards, contained 70% copper 

 & 30% zinc, & was accidentally aspirated by a child who, after 

 developing a cough, vomiting, chills, cyanosis, abdominal distension, 

 & diarrhea, died of acute bronchopneumonia & pulmonary edema, with 

 autopsy appearances of necrosis of the convoluted tubules of the kidney. 

 /Bronze (copper-tin alloy)/ [Browning, E. Toxicity of Industrial Metals. 

 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 148] **PEER 

 REVIEWED** 

 Inhalation of copper fume results in irritation of the upper respiratory 

 tract and an influenza-like illness termed metal fume fever. Signs and 

 symptoms of metal fume fever include chills, muscle aches, nausea, fever, 

 dry throat cough, weakness, and lassitude. There is usually leucocytosis, 

 which may amount to 12,000 to 16,000/ml; recovery is usually rapid, and 

 there are no sequelae. Most workers develop an immunity to these attacks, 

 but it is quickly lost; attacks tend to be more severe on the first day of 

 the work-week. Other effects from copper fume are irritation of the upper 

 respiratory tract, metallic or sweet taste, and in some instances 

 discoloration of the skin and hair. Exposure of workers to concentrations 

 of 1 to 3 mg/cu m for short periods resulted in altered taste response but 

 no nausea; levels of from 0.02 to 0.4 mg/cu m produced no complaints. 

 Transient irritation of the eyes has followed exposure to a fine dust of 

 oxidation products of copper produced in an electric arc. /Copper fume/ 

 [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). 

 NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. 

 DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. 

 Government Printing Office, Jan. 1981.] **PEER REVIEWED** 

 Metal fume fever occurred among workers involved in cutting brass pipes 

 with electric torches in an enclosed, poorly ventilated steam condenser. 

 Symptoms most commonly reported among the 26 workers were fever, dyspnea, 

 chills, headache, and nausea. Fourteen of the workers experienced the 

 symptom of an unusual sweet or metallic taste in the mouth. Clinical signs 

 were limited to wheezing or rales in eight patients; leukocytosis and an 

 elevation of band cell forms were seen in a total of 24 workers. The 

 average time between exposure and onset of symptoms was 5 hr. None of 

 three workers who spent less than 1 hr in the condenser became ill, 

 whereas 25 of the 26 who spent more than 1 hr became ill. Five of 12 

 workers had urine copper levels in excess of 0.05 mg/l /Copper fume/ 

 [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and 

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 Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, 

 NY: John Wiley & Sons Inc., 1993-1994., p. 2004] **PEER REVIEWED** 

 ... Exposure to copper dust at 0.1 mg/cu m causes nausea and metal fume 

 fever, with reversible flu like symptoms. Metal fume fever (also called 

 brass founder's ague) is a transient condition and is characterized by 

 fever, chills, muscle pain, and vomiting. Recovery normally occurs within 

 24 to 48 hr. Tolerance may develop, but is generally lost over the 

 weekend. /Copper dust/ [Clayton, G.D., F.E. Clayton (eds.) Patty's 

 Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: 

 Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., 

 p. 2004] **PEER REVIEWED** 

 IT IS GENERALLY AGREED THAT COPPER ITSELF IS LESS TOXIC THAN ITS SALTS... 

 /CU & CU SALTS/ [Browning, E. Toxicity of Industrial Metals. 2nd ed. 

 New York: Appleton-Century-Crofts, 1969., p. 147] **PEER REVIEWED** 

 Agents assoc with incr risk /of pancreatic cancer/ include ... copper 

 fumes. /copper fumes/ [International Labour Office. Encyclopaedia of 

 Occupational Health and Safety. 4th edition, Volumes 1-4 1998. Geneva, 

 Switzerland: International Labour Office, 1998., p. 4.10] **PEER 

 REVIEWED** 

SKIN, EYE AND RESPIRATORY IRRITATIONS: 

 The fumes and dust cause irritation of the upper respiratory tract. 

 [Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 

 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985., p. 257] 

 **PEER REVIEWED** 

 Inhalation of copper fume results in the irritation of the upper 

 respiratory tract. ... Contact with copper fumes will also cause 

 irritation of the eyes, nose and throat. /Copper fumes/ [Mackison, F. W., 

 R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational 

 Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 

 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 

 2] **PEER REVIEWED** 

 Copper or copper salts may induce allergic contact dermatitis in 

 susceptible individuals. Signs & symptoms include itching, redness, 

 swelling, vesicle formation & pustulation. /Copper or copper salts/ 

 [WHO; Environ Health Criteria 200: Copper p.148 (1998)] **PEER REVIEWED** 

POPULATIONS AT SPECIAL RISK: 

 Persons at special risk include those with impaired pulmonary function, 

 especially those with obstructive airway diseases, since the breathing of 

 copper fume might cause exacerbation of symptoms due to its irritant 

 properties. /Copper fume/ [Mackison, F. W., R. S. Stricoff, and L. J. 

 Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for 

 Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, 

 DC: U.S. Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 Copper dissolved from the wire used in certain intrauterine contraceptive 

 devices has been shown to be absorbed systemically. An appreciable 

 fraction of the copper dissolved from the tubing commonly used in 

 hemodialysis equipment may be retained by the patient ... . [International 

 Labour Office. Encyclopaedia of Occupational Health and Safety. 4th 

 edition, Volumes 1-4 1998. Geneva, Switzerland: International Labour 

 Office, 1998., p. 63.14] **PEER REVIEWED** 

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 STUDY OF THE LITERATURE DESCRIBING SYMPTOMS OCCASIONALLY OBSERVED IN 

 COPPER & BRASS WORKERS WORKERS DOES NOT ALLOW ONE TO CONCLUDE THAT 

 COPPER INTOXICATION IS OCCUPATIONAL DISEASE. SUCH SYMPTOMS ARE DUE TO POOR 

 WORKING CONDITIONS, PRESENCE OF ARSENIC & LEAD AS IMPURITIES ... . 

 [Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, 

 Mass.: Publishing Sciences Group, Inc., 1974., p. 80] **PEER REVIEWED** 

 Copper bracelets are worn as a folk remedy for rheumatic disorders; there 

 is no good evidence to justify such a practice. [Reynolds, J.E.F., Prasad, 

 A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The 

 Pharmaceutical Press, 1982., p. 930] **PEER REVIEWED** 

EVIDENCE FOR CARCINOGENICITY: 

 CLASSIFICATION: D; not classifiable as to human carcinogenicity. BASIS FOR 

 CLASSIFICATION: There are no human data, inadequate animal data from 

 assays of copper compounds, and equivocal mutagenicity data. HUMAN 

 CARCINOGENICITY DATA: None. ANIMAL CARCINOGENICITY DATA: Inadequate. [U.S. 

 Environmental Protection Agency's Integrated Risk Information System 

 (IRIS) on Copper (7440-50-8) Available from: 

 http://www.epa.gov/ngispgm3/iris on the Substance File List as of March 

 15, 2000] **PEER REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 Copper dissolved from the wire used in certain intrauterine contraceptive 

 devices has been shown to be absorbed systemically. An appreciable 

 fraction of the copper dissolved from the tubing commonly used in 

 hemodialysis equipment may be retained by the patient ... . [International 

 Labour Office. Encyclopaedia of Occupational Health and Safety. 4th 

 edition, Volumes 1-4 1998. Geneva, Switzerland: International Labour 

 Office, 1998., p. 63.14] **PEER REVIEWED** 

 STUDY OF THE LITERATURE DESCRIBING SYMPTOMS OCCASIONALLY OBSERVED IN 

 COPPER & BRASS WORKERS WORKERS DOES NOT ALLOW ONE TO CONCLUDE THAT 

 COPPER INTOXICATION IS OCCUPATIONAL DISEASE. SUCH SYMPTOMS ARE DUE TO POOR 

 WORKING CONDITIONS, PRESENCE OF ARSENIC & LEAD AS IMPURITIES ... . 

 [Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, 

 Mass.: Publishing Sciences Group, Inc., 1974., p. 80] **PEER REVIEWED** 

 Copper bracelets are worn as a folk remedy for rheumatic disorders; there 

 is no good evidence to justify such a practice. [Reynolds, J.E.F., Prasad, 

 A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The 

 Pharmaceutical Press, 1982., p. 930] **PEER REVIEWED** 

SKIN, EYE AND RESPIRATORY IRRITATIONS: 

 The fumes and dust cause irritation of the upper respiratory tract. 

 [Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 

 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985., p. 257] 

 **PEER REVIEWED** 

 Inhalation of copper fume results in the irritation of the upper 

 respiratory tract. ... Contact with copper fumes will also cause 

 irritation of the eyes, nose and throat. /Copper fumes/ [Mackison, F. W., 

 R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational 

 Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 

 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 

 2] **PEER REVIEWED** 

 Copper or copper salts may induce allergic contact dermatitis in 

 susceptible individuals. Signs & symptoms include itching, redness, 

 swelling, vesicle formation & pustulation. /Copper or copper salts/ 

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 [WHO; Environ Health Criteria 200: Copper p.148 (1998)] **PEER REVIEWED** 

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The following information was generated from the 

Hazardous Substances Data Bank (HSDB), 

a database of the National Library of Medicine's TOXNET system 

(http://toxnet.nlm.nih.gov) on October 27, 2009. 

Query: The chemical name lead was identified. 

The following terms were added from ChemIDplus: 

olow 

lead flake 

CAS Registry Number: 7439-92-1 

1 

NAME: LEAD, ELEMENTAL 

RN: 7439-92-1 

NOTE: 

 This record contains information for lead in its zero valence state only. 

 For general toxicity and environmental fate of lead ions and lead 

 compounds, refer to the LEAD COMPOUNDS record; for compound-specific 

 information, to the appropriate individual record, e.g., lead iodide, lead 

 phosphate, etc. 

HUMAN HEALTH EFFECTS: 

EVIDENCE FOR CARCINOGENICITY: 

 CLASSIFICATION: B2; probable human carcinogen. BASIS FOR CLASSIFICATION: 

 Sufficient animal evidence. Ten rat bioassays and one mouse assay have 

 shown statisticlly significant increases in renal tumors with dietary and 

 subcutaneous exposure to several soluble lead salts. Animal assays provide 

 reproducible results in several laboratories, in multiple rat strains with 

 some evidence of multiple tumor sites. Short term studies show that lead 

 affects gene expression. Human evidence is inadequate. HUMAN 

 CARCINOGENICITY DATA: Inadequate. ANIMAL CARCINOGENICITY DATA: Sufficient. 

 /Lead and compounds/ [U.S. Environmental Protection Agency's Integrated 

 Risk Information System (IRIS) on Lead and compounds (inorganic) 

 (7439-92-1) Available from: http://www.epa.gov/ngispgm3/iris on the 

 Substance File List as of March 15, 2000] **PEER REVIEWED** 

 A3; Confirmed animal carcinogen with unknown relevance to humans. /Lead, 

 elemental, and inorganic compounds, as Pb/ [American Conference of 

 Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values 

 for Chemical Substances and Physical Agents and Biological Exposure 

 Indices. Cincinnati, OH, 2008, p. 36] **QC REVIEWED** 

 Lead, lead compounds: Reasonably anticipated to be a human carcinogen 

 [DHHS/National Toxicology Program; Eleventh Report on Carcinogens: Lead, 

 and Lead Compounds (January 2005). Available from, as of July 31, 2009: 

 http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s101lead.pdf ] **QC 

 REVIEWED** 

HUMAN TOXICITY EXCERPTS: 

 TOXIC BY INGESTION & INHALATION OF DUST OR FUME. [Sax, N.I. and R.J. 

 Lewis, Sr. (eds.). Hawley's Condensed Chemical Dictionary. 11th ed. New 

 York: Van Nostrand Reinhold Co., 1987., p. 687] **PEER REVIEWED** 

 SEVERE POISONING IS PRODUCED THROUGH EXPOSURE TO FUMES FROM LEAD FURNACES 

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 IF FUMES ARE ALLOWED TO ESCAPE & FROM DUST FROM DROSSING. [Hamilton, 

 A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: 

 Publishing Sciences Group, Inc., 1974., p. 88] **PEER REVIEWED** 

 MOST ... LEAD EXPOSURE STUDIES INVOLVE LEAD OXIDE DUST OR THE FUME OF 

 METALLIC LEAD. SOME REPORTS HAVE INDICATED THAT THE DUSTS OF CERTAIN 

 INSOLUBLE LEAD COMPOUNDS, SUCH AS THE SULFIDE & CHROMATE, WERE LESS 

 HAZARDOUS THAN MORE SOLUBLE FORMS OF LEAD. [American Conference of 

 Governmental Industrial Hygienists, Inc. Documentation of the Threshold 

 Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. 

 Cincinnati, OH: ACGIH, 1991., p. 848] **PEER REVIEWED** 

 ONE OF 2 /EPIDEMIOLOGICAL/ STUDIES ON METALLIC LEAD WORKERS SHOWED NO 

 EXCESS OF CANCER DEATHS. THE OTHER SHOWED A SLIGHT (ALTHOUGH SIGNIFICANT) 

 EXCESS OF DEATHS DUE TO CANCERS OF DIGESTIVE SYSTEM & RESP SYSTEM 

 AMONG SMELTER WORKERS BUT NOT AMONG WORKERS IN LEAD-ACID BATTERY FACTORY. 

 AS 60% OF MEMBERS OF SMELTER WORKERS COHORT WERE HIRED AFTER 1950, FURTHER 

 FOLLOW-UP OF THIS COHORT IS WARRANTED, IN ORDER TO DETERMINE MORE RELIABLY 

 IF THERE IS AN EXCESS RISK. [IARC. Monographs on the Evaluation of the 

 Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, 

 International Agency for Research on Cancer, 1972-PRESENT. (Multivolume 

 work)., p. V23 387 (1980)] **PEER REVIEWED** 

 Cases of lead poisoning due to retained bullets are reported only rarely 

 but represent potentially life-threatening reactions. ... Almost all cases 

 in USA have involved the dissolution of a single bullet over several mo to 

 more than 20 yr. ... Bullets in joint spaces are ... more likely to cause 

 toxic complications than are bullets lodged in soft tissues. [Gosselin, 

 R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 

 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-227] **PEER 

 REVIEWED** 

 LEAD METAL FOREIGN BODIES IN EYE OR ... ORBIT IN HUMANS ... HAVE BEEN 

 CONSIDERED TO CAUSE LITTLE REACTION & RARELY ANY TOXIC EFFECT. 

 CLINICAL EXPERIENCES WITH VARIOUS INTRAOCULAR FOREIGN BODIES PRESENTED IN 

 DETAIL WITH HISTOLOGIC STUDIES ... INDICATED THAT LEAD METALLIC FOREIGN 

 BODIES CAUSED MINIMAL INFLAMMATORY REACTION, MAINLY MECHANICAL INJURY. ... 

 /IN ANOTHER REPORT IT WAS/ CONCLUDED THAT LEAD FRAGMENTS IN PATIENTS WERE 

 WELL TOLERATED IN THE EYE & IN THE ORBIT & THAT THEY SHOULD NOT BE 

 REMOVED UNLESS THEY WERE IN THE ANTERIOR CHAMBER. ... /A/ CASE /IS 

 DESCRIBED/ IN WHICH ... A SMALL LEAD SHOT WAS ALLOWED TO REMAIN IN THE 

 VITREOUS, THE VISION RETURNED TO NORMAL AS BLOOD IN THE VITREOUS ABSORBED 

 OR SETTLED IN THE COURSE OF A YEAR. ... IN ONE CASE, WHICH APPEARS TO HAVE 

 BEEN QUITE EXCEPTIONAL ... A PATIENT WITH A LEAD SHOT BEHIND ONE GLOBE HAD 

 IMPAIRED VISION IN THAT EYE. THIS WAS ASSUMED TO BE DUE TO A TOXIC EFFECT 

 OF LEAD. WHETHER THIS INTERPRETATION WAS CORRECT OR NOT, A SIGNIFICANT 

 IMPROVEMENT OF VISION WAS REPORTED WHEN SYSTEMIC & TOPICAL TREATMENT 

 WITH 2,3-DIMERCAPTOPROPANSULFONATE SODIUM WAS STARTED 5 YEARS AFTER THE 

 INJURY. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: 

 Charles C. Thomas Publisher, 1986., p. 548] **PEER REVIEWED** 

 In a cross-sectional study, the neurobehavioral effects of low-level lead 

 exposure were evaluated in a group of 59 lead workers compared with 59 

 matched controls. The groups were not significantly different in age, 

 education level, sleep pattern, or use of alcohol. The mean blood lead 

 level in the exposed group was 2.37 umol/l (50 ug/100 ml) which was 

 similar to the previous three years (2.36, 2.36, and 2.32 umol/l, 

 respectively). The mean duration of exposure was 8109 hrs. Visual sensory 

 function was affected, and perhaps as a consequence sustained attention 

 and psychomotor tasks were performed more slowly by the lead exposed 

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 group. Cognitive functions were also impaired, with sensory store and 

 short term memories, and learning abilities all showing deficits in lead 

 workers. Multiple linear regression analysis relating to lead workers test 

 performance and their lead exposure showed that performance on the sensory 

 store memory test alone was significantly related to exposure. [Williamson 

 AM, Teo RKC; Br J Ind Med 43: 374-80 (1986)] **PEER REVIEWED** 

 The activities of erythrocyte (rbc) arginase, pyrimidine 5'- nucleotidase 

 (P5N), and deoxypyrimidine 5'-nucleotidase (dP5N) were compared in 16 lead 

 workers and 14 age-matched controls as correlates of blood lead (PbB) and 

 unextracted zinc protoporphyrin (EP). Subjects with blood lead of 0.9-2.5 

 uM (19-52 ug/dl) had 6.5 + or - 0.6 IU of pyrimidine 5'-nucleotidase 

 activity with uridine monophosphate (UMP) as substrate, significantly less 

 (p < 0.001) than the 12.0 + or - 0.7 IU activity of controls with blood 

 lead 0.3-0.6 uM (6-12 ug/dl). Erythrocyte pyrimidine 5'-nucleotidase was 

 significantly correlated with blood lead (r= 0.75). There were no 

 significant differences in erythrocyte arginase or deoxypyrimidine 

 5'-nucleotidase activity. [Cook LR et al; Br J Ind Med 43: 387-90 (1986)] 

 **PEER REVIEWED** 

 In a cross-sectional study of 20 gun-metal foundry workers (mean age 47 

 yr) the subclinical neurophysiological effects of exposure to lead, zinc, 

 copper, and tin were evaluated by "short-latency" somatosensory evoked 

 potential (SSEP). Controls were age and height-matched males without 

 occupational exposure to lead. Range of employment was 1-16 yr (mean 10 

 yr). In exposed workers, mean blood lead was 42 ug/dl, mean zinc plasma 95 

 ug/dl, mean copper plasma 105 ug/dl, and mean urinary tin 28 ug/l. In 

 workers, the interpeak latency of SSEP in the cervico-spino-bulbar region 

 (N9(Erb)-N13 latency) was significantly prolonged (p < 0.05), and the 

 MCV and SCV in the forearm were significantly slowed (0.01 < p < 0.05) 

 when compared with controls. The yield of urinary lead following challenge 

 with Ca-EDTA was positively related to SSEP latency in the 

 cervico-spino-bulbar region and inversely related to hematocrit (p < 

 0.05). The interpeak latency in the upper central nervous system (N13-20 

 latency) was inversely related to zinc concentration in erythrocytes. 

 Latency up to the Erbs point was inversely related to urinary zinc. MCV 

 and SCV in the palm were positively related to erythrocyte zinc 

 concentration and plasma copper concentration, respectively (p < 0.05). 

 It appears that zinc antagonizes the central and peripheral 

 neurophysiologic dysfunction caused by lead, and similarly copper 

 antagonizes the peripheral sensory nerve dysfunction. [Araki S et al; Am J 

 Ind Med 10: 163-75 (1986)] **PEER REVIEWED** 

 Battery workers (N= 18), who were exposed to high airborne lead levels, 

 /were compared/ with cement workers (N= 18), who were exposed to ambient 

 lead levels. Blood lead urinary lead, semen lead, and zinc protoporphyrin 

 concentrations were markedly elevated (p < 0.001) in battery workers. 

 Battery workers had a significantly shifted (p < 0.025) frequency 

 distribution of sperm count (median count, 45 vs 73x10x6 cells/cc, 

 respectively). ... These results suggest a direct toxic effect of 

 increased lead absorption on sperm production or transport in man. 

 [Assennato G et al; Arch Environ Health 42 (2): 124 (1987)] **PEER 

 REVIEWED** 

 Lead containing particles in ambient air have an aerodynamic diameter of 

 approx 0.1-1.0 um, & the predicted deposition in the airway is about 

 35%. This is questionable for smaller particles ( < 0.1 um) which are 

 mainly deposited by diffusion. Actual measurements of deposition in human 

 volunteers gave results that differed considerably depending on the 

 physical & chemical properties of the inhaled aerosol. ... A 

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 deposition of approx 25% /was observed/ after exposure to particles with a 

 mass median aerodynamic diameter of 0.25 um. ... A deposition in the resp 

 tract of about 60% /was observed/ in persons close to a motorway, where 

 particles were about 0.03 um in diameter. This figure is consistent with 

 lab expt carried out by the same authors, in which subjects inhaled 

 radioactively labeled particles of about the same size. When volunteers 

 inhaled lead particles near urban roads where the particle size was larger 

 (0.2-2.0 um), deposition was about 50%. Based on available data, it seems 

 reasonable to conclude that the rate of deposition of airborne lead in the 

 general population is approx 30-50%, depending on particle size & 

 ventilation rates. [Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, 

 V.B. (eds). Handbook of the Toxicology of Metals. 2nd ed. Vols I, II.: 

 Amsterdam: Elsevier Science Publishers B.V., 1986., p. V2 311] **PEER 

 REVIEWED** 

 There is no evidence that inhaled lead /as a trace substance in the 

 environment/ has local effects on the respiratory system in man ... . 

 [Friberg, L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook 

 of the Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier 

 Science Publishers B.V., 1986., p. V2 324] **PEER REVIEWED** 

 Dissolution of lead from lead soldered joints in water pipes frequently 

 occurs where water is soft or acidic. /SRP: Thereby contributing to long 

 term chronic exposure to the general population./ [Evans RD, Rigler FH; 

 Water Air Soil Pollution 24: 141-51 (1985)] **PEER REVIEWED** 

 Most lead poisoning in children occurs between ages 1 and 5 years. There 

 is a higher incidence of child-related lead poisoning during the warmer 

 months. [Gossel, T.A., J.D. Bricker. Principles of Clinical Toxicology. 

 3rd ed. New York, NY: Raven Press, Ltd., 1994., p. 192] **PEER REVIEWED** 

 Chronic exposure to lead has been found to produce infertility, germinal 

 epithelium damage, oligospermia and testicular degeneration, decreased 

 sperm motility, and prostatic hyperplasia. [Thomas, J.A., K.S. Korach, 

 J.A. McLachlan. Endocrine Toxicology. New York, NY: Raven Press, Ltd., 

 1985., p. 167] **PEER REVIEWED** 

 There is convincing evidence that lead is transferred to neonates via 

 maternal milk. It appears that maternal milk might be a source of lead for 

 the neonates, particularly when metal levels are elevated in the mother. 

 [Thomas, J.A., K.S. Korach, J.A. McLachlan. Endocrine Toxicology. New 

 York, NY: Raven Press, Ltd., 1985., p. 168] **PEER REVIEWED** 

 Arthralgia, often associated with muscle aches and pain, is a frequent 

 symptom in lead poisoning. Although generally thought to appear mainly in 

 chronic poisoning, joint pain is often reported even by persons exposed 

 briefly (weeks) who have relatively low blood lead concentrations. It is a 

 symptom that ... frequently indicates that the blood lead concentration is 

 on the rise. [Rom, W.N. (ed.). Environmental and Occupational Medicine. 

 2nd ed. Boston, MA: Little, Brown and Company, 1992., p. 744] **PEER 

 REVIEWED** 

 ... The EPA concluded that blood levels in the range of 50-70 ug/dl are 

 associated with a 5-point reduction in IQ, even among asymptomatic 

 children and after controlling for potential confounding factors. [Rom, 

 W.N. (ed.). Environmental and Occupational Medicine. 2nd ed. Boston, MA: 

 Little, Brown and Company, 1992., p. 1233] **PEER REVIEWED** 

 /Researchers/ reported on a cohort of 132 young adults whose levels of 

 dentine lead were measured in primary school. Young people whose childhood 

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 dentine levels were greater than 20 ppm were found to be at a markedly 

 higher risk of dropping out of high school and having reading 

 disabilities, than the low-lead exposure group, whose dentine lead levels 

 had been less than 10 ppm. Other measures of performance affected included 

 vocabulary and grammatical reasoning, absenteeism, hand-eye coordination 

 (poorer) and reaction time (slowed). [Rom, W.N. (ed.). Environmental and 

 Occupational Medicine. 2nd ed. Boston, MA: Little, Brown and Company, 

 1992., p. 1234] **PEER REVIEWED** 

 The earliest subjective symptoms /of lead poisoningin working adults/ are 

 diffuse and include weariness at the end of the day. The patient is moody 

 and irritable and may fall asleep watching television. Often he loses his 

 interest in leisure-time activities. Such mild symptoms frequently occur 

 with blood-lead levels below 80 ug/100 ml. [Zenz, C., O.B. Dickerson, E.P. 

 Horvath. Occupational Medicine. 3rd ed. St. Louis, MO., 1994, p. 518] 

 **PEER REVIEWED** 

 ... 49 long-term lead-exposed workers were compared to 27 low-exposed 

 workers through a number of psychologic tests. After controlling for age, 

 the exposed group performed worse on tests measuring memory, learning, and 

 reaction time, while impaired performance was not detected in reasoning, 

 perceptual speed, and psychomotor ability. [Zenz, C., O.B. Dickerson, E.P. 

 Horvath. Occupational Medicine. 3rd ed. St. Louis, MO., 1994, p. 782] 

 **PEER REVIEWED** 

 ... /Researchers/ found impaired performances on tests of verbal concept 

 formation, perceptual performance, and memory in a lead-exposed group with 

 present lead concentrations between 40 and 60 ug/100 ml. [Zenz, C., O.B. 

 Dickerson, E.P. Horvath. Occupational Medicine. 3rd ed. St. Louis, MO., 

 1994, p. 782] **PEER REVIEWED** 

 A study of 260 infants prospectively followed from birth suggests that the 

 expected stature of a child born to a mother with a prenatal blood lead 

 concentration over 7.7 ug/dL is about 2 cm shorter at 15 mos of age if, 

 potentially, the infant also incurred a 10 ug/dL blood level increase 

 during the 3- to 15-month interval of life. [Ellenhorn, M.J., S. 

 Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: 

 Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: 

 Williams and Wilkins, 1997., p. 1565] **PEER REVIEWED** 

 Moderate effects on follicle stimulating hormone and luteinizing hormone 

 have been correlated with lead levels over about 50 ug/dL. [Ellenhorn, 

 M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical 

 Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, 

 MD: Williams and Wilkins, 1997., p. 1565] **PEER REVIEWED** 

 The relative risk of preterm delivery at exposure levels of 14 ug/dL or 

 greater was 8.7 times the risk at levels of up to 8 ug/dL in one 

 prospective study. A Cincinnati study noted a half-week's reduction in 

 gestation for every 10 ug/dL increment in blood lead. [Ellenhorn, M.J., S. 

 Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: 

 Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: 

 Williams and Wilkins, 1997., p. 1565] **PEER REVIEWED** 

 Lead has an adverse effect on fetuses, particularly in the later stages of 

 development. Distribution of lead in fetal tissues was examined in a case 

 in which a woman was exposed during pregnancy. The female worker was 

 exposed to lead dust for 8 hr daily when conception occurred. ... 

 Measurements of lead content were started after the end of the exposure 

 and continued for 6 months until normal values were obtained. Because of 

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 half-life of nearly 20 days for lead elimination from blood, the estimated 

 body burden at the end of exposure was about 1200 ppb. The fetal tissue 

 samples contained between 0.4 (brain) and 7.9 (liver) ug Pb/g dry weight. 

 The fetal lead was stored mainly in bone, blood, and liver. [Clayton, 

 G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. 

 Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John 

 Wiley & Sons Inc., 1993-1994., p. 2073] **PEER REVIEWED** 

 Goyer found inclusion bodies in renal biopsies of two lead industry 

 workers who had excess lead exposure, but only subclinical signs of lead 

 toxicity in the form of weakness, nausea, some abdominal colic, and blood 

 lead values of about 100 ug/dl. [Clayton, G.D., F.E. Clayton (eds.) 

 Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: 

 Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., 

 p. 2073] **PEER REVIEWED** 

 Finnish men were biologically monitored for lead exposure. The cases (213 

 spontaneous abortions) and controls (300 births) were identified from 

 medical registers in Finland. The results did not show a statistically 

 significant relationship between spontaneous abortion and paternal lead 

 exposure among all the study subjects. However, a significant increase in 

 the risk of those women whose husbands had been monitored (blood lead 

 equal to or greater than 1.5 umol/l) during or close to the time of 

 spermatogenesis was observed. [Clayton, G.D., F.E. Clayton (eds.) Patty's 

 Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: 

 Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., 

 p. 2081] **PEER REVIEWED** 

 Small increases in blood pressure have been related to adults with PbB 

 levels down to 7 ug/dl. [American Conference of Governmental Industrial 

 Hygienists, Inc. Documentation of the Threshold Limit Values and 

 Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: 

 ACGIH, 1991., p. 849] **PEER REVIEWED** 

 ... PbB concentrations in excess of 60 ug/100 g ... have been associated 

 with peripheral neuropathy, gastrointestinal disturbances and anemia. ... 

 Nerve conduction velocities ... /decreases/ in workers with maximal blood 

 leads between 50 and 70 ug/100 g. [American Conference of Governmental 

 Industrial Hygienists, Inc. Documentation of the Threshold Limit Values 

 and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, 

 OH: ACGIH, 1991., p. 849] **PEER REVIEWED** 

 Food and Environmental Agents: Effect on Breast-Feeding: Reported Sign or 

 Symptom in Infant or Effect on Lactation: Lead: Possible neurotoxicity. 

 /From Table 7/ [Report of the American Academy of Pediatrics Committee on 

 Drugs in Pediatrics 93 (1): 142 (1994)] **PEER REVIEWED** 

MEDICAL SURVEILLANCE: 

 ... Comparative advantages of /the biological indicator/ 

 delta-aminolevulinic acid dehydratase in typical (variable) occupational 

 exposure conditions included: the highest sensitivity at low and 

 relatively high lead (Pb) exposure levels; better reflection of 

 biologically active Pb as opposed to blood lead (particularly compared to 

 delta-aminolevulinic acid and coproporphyrin); higher specificity compared 

 to other indicators of Pb effect; and generally higher reliability with 

 regard to biologically and methodologically induced variations. ... 

 [Telisman S et al; Int Arch Occup Environ Health 50 (4): 397-412 (1982)] 

 **PEER REVIEWED** 

POPULATIONS AT SPECIAL RISK: 

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 SRP: Law enforcement officers are subject to potential intoxication while 

 firing weapons in an indoor firing range. **PEER REVIEWED** 

 Lead toxicity is of special concern to workers, such as miners and 

 smelters, automobile finishers, foundry and storage battery workers, 

 typesetters, sheet metal workers, and spray painters. Lead ... may also be 

 a contaminant in moonshine whiskey. [Gossel, T.A., J.D. Bricker. 

 Principles of Clinical Toxicology. 3rd ed. New York, NY: Raven Press, 

 Ltd., 1994., p. 191] **PEER REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 ... MOST SEVERE HAZARD OCCURS IN SPRAYING OF MOLTEN LEAD ... GRINDING OR 

 POWER SANDING ... SOLDER & POURING OF LEADED IRON & STEEL ... 

 MIXING & WEIGHING OF LEAD POWDERS. [Browning, E. Toxicity of 

 Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 

 173] **PEER REVIEWED** 

 PRINCIPAL TYPES OF PRIMARY INDUSTRIES WITH OCCUPATIONAL EXPOSURE ... ARE 

 LEAD SMELTING & REFINING, STORAGE BATTERY MANUFACTURE, WELDING & 

 STEEL CUTTING & PRINTING. HIGHEST EXPOSURES ... OCCUR IN SMELTING 

 & REFINING OF LEAD. MOLTEN LEAD & LEAD ALLOYS ARE BROUGHT TO HIGH 

 TEMP, RESULTING IN VAPORIZATION OF LEAD. [IARC. Monographs on the 

 Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World 

 Health Organization, International Agency for Research on Cancer, 

 1972-PRESENT. (Multivolume work)., p. V23 345 (1980)] **PEER REVIEWED** 

EVIDENCE FOR CARCINOGENICITY: 

 CLASSIFICATION: B2; probable human carcinogen. BASIS FOR CLASSIFICATION: 

 Sufficient animal evidence. Ten rat bioassays and one mouse assay have 

 shown statisticlly significant increases in renal tumors with dietary and 

 subcutaneous exposure to several soluble lead salts. Animal assays provide 

 reproducible results in several laboratories, in multiple rat strains with 

 some evidence of multiple tumor sites. Short term studies show that lead 

 affects gene expression. Human evidence is inadequate. HUMAN 

 CARCINOGENICITY DATA: Inadequate. ANIMAL CARCINOGENICITY DATA: Sufficient. 

 /Lead and compounds/ [U.S. Environmental Protection Agency's Integrated 

 Risk Information System (IRIS) on Lead and compounds (inorganic) 

 (7439-92-1) Available from: http://www.epa.gov/ngispgm3/iris on the 

 Substance File List as of March 15, 2000] **PEER REVIEWED** 

 A3; Confirmed animal carcinogen with unknown relevance to humans. /Lead, 

 elemental, and inorganic compounds, as Pb/ [American Conference of 

 Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values 

 for Chemical Substances and Physical Agents and Biological Exposure 

 Indices. Cincinnati, OH, 2008, p. 36] **QC REVIEWED** 

 Lead, lead compounds: Reasonably anticipated to be a human carcinogen 

 [DHHS/National Toxicology Program; Eleventh Report on Carcinogens: Lead, 

 and Lead Compounds (January 2005). Available from, as of July 31, 2009: 

 http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s101lead.pdf ] **QC 

 REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 ... MOST SEVERE HAZARD OCCURS IN SPRAYING OF MOLTEN LEAD ... GRINDING OR 

 POWER SANDING ... SOLDER & POURING OF LEADED IRON & STEEL ... 

 MIXING & WEIGHING OF LEAD POWDERS. [Browning, E. Toxicity of 

 Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 

 173] **PEER REVIEWED** 

 PRINCIPAL TYPES OF PRIMARY INDUSTRIES WITH OCCUPATIONAL EXPOSURE ... ARE 

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 LEAD SMELTING & REFINING, STORAGE BATTERY MANUFACTURE, WELDING & 

 STEEL CUTTING & PRINTING. HIGHEST EXPOSURES ... OCCUR IN SMELTING 

 & REFINING OF LEAD. MOLTEN LEAD & LEAD ALLOYS ARE BROUGHT TO HIGH 

 TEMP, RESULTING IN VAPORIZATION OF LEAD. [IARC. Monographs on the 

 Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World 

 Health Organization, International Agency for Research on Cancer, 

 1972-PRESENT. (Multivolume work)., p. V23 345 (1980)] **PEER REVIEWED** 

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The following information was generated from the 

Hazardous Substances Data Bank (HSDB), 

a database of the National Library of Medicine's TOXNET system 

(http://toxnet.nlm.nih.gov) on October 27, 2009. 

Query: The chemical name mercury was identified. 

The following terms were added from ChemIDplus: 

quecksilber 

mercurio 

mercure 

liquid silver 

kwik 

hydrargyrum 

colloidal mercury 

CAS Registry Number: 7439-97-6 

1 

NAME: MERCURY, ELEMENTAL 

RN: 7439-97-6 

NOTE: 

 This record contains information for mercury in its zero valence state 

 only. For general toxicology and environmental fate of the mercury ions 

 and inorganic mercury compounds, refer to the MERCURY COMPOUNDS record; 

 for compound-specific information, refer to the appropriate individual 

 records, e.g., mercuric oxide, mercurous oxide, etc. 

HUMAN HEALTH EFFECTS: 

TOXICITY SUMMARY: 

 IDENTIFICATION: In its elemental form, mercury is a heavy silvery liquid 

 at room temperature and has a very high vapour pressure. Mercury vapor is 

 more soluble in plasma, whole blood, and hemoglobin than in distilled 

 water, where it dissolves only slightly. The major natural sources of 

 mercury are degassing of the earth's crust, emissions from volcanoes, and 

 evaporation from natural bodies of water. (The world-wide mining of 

 mercury is estimated to yield about 10,000 tons per year. The activities 

 lead to some losses of mercury and direct discharges to the atmosphere). 

 Other important sources are fossil fuel combustion, metal sulfide ore 

 smelting, gold refining, cement production, refuse incineration, and 

 industrial applications of metals. A major use of mercury is as a cathode 

 in the electrolysis of sodium chloride. Mercury is used in the electrical 

 industry, in control instruments in the home and industry, and in 

 laboratory and medical instruments. A very large amount of mercury is used 

 for the extraction of gold. Dental silver amalgam for tooth filling 

 contains large amounts of mercury. Use of skin-lightening soap and creams 

 can give rise to substantial mercury exposure. Occupational exposure to 

 inorganic mercury has been investigated in chloralkali plants, mercury 

 mines, thermometer factories, refineries, and in dental clinics. High 

 mercury levels have been reported for all these occupational exposure 

 situations, although levels vary according to work environment conditions. 

 HUMAN EXPOSURE: The general population is primarily exposed to mercury 

 through the diet and dental amalgam. Acute inhalation exposure to mercury 

 vapor may be followed by chest pains, dyspnea, coughing, hemoptysis, and 

 sometimes interstitial pneumonitis leading to death. (The ingestion of 

 mercuric compounds, in particular mercuric chloride, has caused ulcerative 

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 gastroenteritis and acute tubular necrosis causing death from anuria where 

 dialysis was not available). The central nervous system is the critical 

 organ for mercury vapor exposure. Subacute exposure has given rise to 

 psychotic reactions characterized by delerium, hallucinations, and 

 suicidal tendency. Occupational exposure has resulted in erethism as the 

 principal feature of a broad ranging functional disturbance. The kidney is 

 the critical organ following the ingestion of inorganic divalent mercury 

 salts. Occupational exposure to metallic mercury has long been associated 

 with the development of proteinuria. Both metallic mercury vapor and 

 mercury compounds have given rise to contact dermatitis. Mercurial 

 pharmaceuticals have been responsible for Pink disease (acrodynia) in 

 children, and mercury vapor exposure may be a cause of "Kawasaki" disease. 

 Results of both human and animal studies indicate that about 80% of 

 inhaled metallic mercury vapour is retained by the body, whereas liquid 

 metallic mercury is poorly absorbed via the gastrointestinal tract. ANIMAL 

 STUDIES: Evidence of damage to brain, kidney, heart, and lungs have been 

 reported in rabbits exposed acutely to metallic mercury vapor at certain 

 concentrations. Both reversible and irreversible toxic effects may be 

 caused by mercury and its compounds. In two studies, tremor and 

 behavioural effects were observed in rabbits and rats after several weeks 

 of exposure to metallic mercury vapour. Depending upon the animal strain 

 tested, either auto-immunity or immunosuppression is observed. The most 

 sensitive adverse effect caused by mercuric mercury is the formation of 

 mercuric-mercury-induced auto-immune glomerulonephritis. Mercuric chloride 

 was found to induce gene mutations in mouse lymphoma cells and DNA damage 

 in rat and mouse fibroblasts. The World Health Organization reported no 

 evidence that inorganic mercury is carcinogenic. The neurotoxic effect 

 seen after exposure to metallic mercury vapour is attributable to the 

 divalent mercury ion formed through oxidation in the brain tissue. 

 Significantly more mercury is transported to the brain of mice and monkeys 

 after the inhalation of elemental mercury than after the intravenous 

 injection of equivalent doses of the mercuric form. [World Health 

 Organization/International Programme on Chemical Safety. Environmental 

 Health Criteria 118 Inorganic Mercury. pp. 13-21, 68-83 (1991)] **PEER 

 REVIEWED** 

EVIDENCE FOR CARCINOGENICITY: 

 CLASSIFICATION: D; not classifiable as to human carcinogenicity. BASIS FOR 

 CLASSIFICATION: Based on inadequate human and animal data. Epidemiologic 

 studies failed to show a correlation between exposure to elemental mercury 

 vapor and carcinogenicity; the findings in these studies were confounded 

 by possible or known concurrent exposures to other chemicals, including 

 human carcinogens, as well as lifestyle factors (e.g., smoking). Findings 

 from genotoxicity tests are severely limited and provide equivocal 

 evidence that mercury adversely affects the number or structure of 

 chromosomes in human somatic cells. HUMAN CARCINOGENICITY DATA: 

 Inadequate. ANIMAL CARCINOGENICITY DATA: Inadequate. [U.S. Environmental 

 Protection Agency's Integrated Risk Information System (IRIS) on Mercury 

 (Inorganic ) (7439-97-6) Available from: http://www.epa.gov/ngispgm3/iris 

 on the Substance File List as of March 15, 2000] **PEER REVIEWED** 

 Evaluation: There is inadequate evidence in humans for the carcinogenicity 

 of mercury and mercury compounds. There is inadequate evidence in 

 experimental animals for the carcinogenicity of metallic mercury. There is 

 limited evidence in experimental animals for the carcinogenicity of 

 mercuric chloride. There is sufficient evidence in experimental animals 

 for the carcinogenicity of methylmercury chloride. In making the overall 

 evaluation, the Working Group took into account evidence that 

 methylmercury compounds are similar with regard to absorption, 

 distribution, metabolism, excretion, genotoxicity and other forms of 

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 toxicity. Overall evaluation: Methylmercury compounds are possibly 

 carcinogenic to humans (Group 2B). Metallic mercury and inorganic mercury 

 compounds are not classifiable as to their carcinogenicity to humans. 

 (Group 3). /Mercury and mercury compounds/ [IARC. Monographs on the 

 Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World 

 Health Organization, International Agency for Research on Cancer, 

 1972-PRESENT. (Multivolume work)., p. V58 324 (1993)] **PEER REVIEWED** 

 A4: Not classifiable as a human carcinogen. /Mercury, elemental and 

 inorganic forms, as Hg/ [American Conference of Governmental Industrial 

 Hygienists TLVs and BEIs. Threshold Limit Values for Chemical Substances 

 and Physical Agents and Biological Exposure Indices. Cincinnati, OH, 2008, 

 p. 37] **QC REVIEWED** 

HUMAN TOXICITY EXCERPTS: 

 Aneuploidy and other chromosomal aberrations have been observed in 

 lymphocytes from whole blood cultures of workers occupationally exposed to 

 mercury, including people working with mercury amalgams. [USEPA; Mercury 

 Health Effects Update p.5-11 (1984) EPA 600/8-84-019F] **PEER REVIEWED** 

 Humans exposed occupationally to metallic mercury cmpd or Hg amalgams had 

 significantly increased occurrence of lymphocytic aneuploidy but not 

 structural chromosome aberrations relative to controls. [Nat'l Research 

 Council Canada; Effect of Mercury in the Canadian Environment p.115 (1979) 

 NRCC No. 16739] **PEER REVIEWED** 

 The case of a 25 yr old woman with previous metallic mercury skin deposits 

 treated by excision of the affected area and oral administration of 125 mg 

 penicillamine 2 times/day, is reported. Symptoms of metallic mercury 

 intoxication were not shown. Biopsy of the lumps produced a salmon pink 

 fluid containing globules of metallic mercury. One yr after the incident 

 no signs of long term intoxication were shown. [Grounds RM; J R Soc Med 

 77: 611-13 (1984)] **PEER REVIEWED** 

 CHRONIC ABSORPTION FROM HANDLING OF MERCURY OR EXPOSURE TO ITS VAPORS HAS 

 LED TO A CHARACTERISTIC DISCOLORATION OF THE FRONT SURFACE OF THE LENS. 

 ... ROSE-BROWN OR PINKISH HOMOGENEOUS REFLEX IS SEEN ... IN SOME CASES 

 INVOLVING WHOLE ANTERIOR SURFACE ... SOMETIMES ... ANTERIOR SUBCAPSULAR 

 DISC. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles 

 C. Thomas Publisher, 1986., p. 583] **PEER REVIEWED** 

 Neonates have absorbed significant amounts of mercury after the breakage 

 of elemental mercury switches in their incubators. [Ellenhorn, M.J. and 

 D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human 

 Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 

 1048] **PEER REVIEWED** 

 67 patients with oral lichen plantus of the atrophic-erosive or reticular 

 plaque type were examined. Dental amalgam in contact with mucosal lesions 

 was present in 64 patients, and gold fillings in 33. Patch testing with a 

 standard procedure was performed with components of dental fillings. 11 

 patients (16%) reacted to at least one of the mercury compounds as 

 compared to 8% in a reference group. Most positive reactions were caused 

 by elemental mercury and ammoniated mercury. [Mobacken H et al; Contact 

 Dermatitis 10 (1): 11-5 (1984)] **PEER REVIEWED** 

 Increased metabolic rate increases ... food consumption and exposure to 

 mercury through the food chain. [USEPA; Ambient Water Quality Criteria 

 Doc: Mercury p.12 (1984) EPA 440/5-84-026] **PEER REVIEWED** 

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 AMONG INORG CMPD, ELEMENTAL MERCURY & DIVALENT MERCURY SALT ARE ... OF 

 TOXICOLOGICAL INTEREST. IT IS DOUBTFUL WHETHER MERCUROUS MERCURY HAS ANY 

 SURVIVAL IN THE ORGANISM, ALTHOUGH AT PRESENT POSSIBILITY ... THAT 

 MERCUROUS MERCURY MAY BE INT IN REDOX TRANSFORMATION OF ELEMENTAL & 

 MERCURIC MERCURY OR VICE VERSA IN BODY. [Friberg, L., Nordberg, G.F., 

 Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 

 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986., 

 p. 389] **PEER REVIEWED** 

 DISTURBANCES OF EYES IN MERCURY POISONING CONSISTS OF DISCOLORATION OF 

 CORNEA & LENS, TREMOR OF EYELIDS, & POSSIBLY ... DISTURBANCES OF 

 VISION & EXTRAOCULAR MUSCLES. ... IN VERY YOUNG CHILDREN ACRODYNIA. 

 ... CHARACTERTISTIC BY OCULAR SYMPTOMS ... PHOTOPHOBIA ... CONJUNCTIVITIS, 

 ITCHING ... KERATITIS ... [Grant, W.M. Toxicology of the Eye. 3rd ed. 

 Springfield, IL: Charles C. Thomas Publisher, 1986., p. 583] **PEER 

 REVIEWED** 

 CHRONIC ABSORPTION ... HANDLING MERCURY OR EXPOSURE TO ITS VAPORS HAS LED 

 TO A CHARACTERISTIC DISCOLORATION OF THE FRONT SURFACE OF THE LENS. ... 

 ROSE-BROWN OR PINKISH HOMOGENEOUS REFLEX IS SEEN ... IN SOME CASES 

 INVOLVING WHOLE ANTERIOR SURFACE ... SOMETIMES ... ANTERIOR SUBCAPSULAR 

 DISC. /MERCURY/ [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, 

 IL: Charles C. Thomas Publisher, 1986., p. 583] **PEER REVIEWED** 

 AMONG INORG CMPD, ELEMENTAL MERCURY & DIVALENT MERCURY SALT ARE THE 

 CMPD OF TOXICOLOGICAL INTEREST. IT IS DOUBTFUL WHETHER MERCUROUS MERCURY 

 HAS ANY SURVIVAL IN THE ORGANISM, ALTHOUGH AT PRESENT POSSIBILITY ... THAT 

 MERCUROUS MERCURY MAY BE INTERMEDIATE IN REDOX TRANSFORMATION OF ELEMENTAL 

 & MERCURIC MERCURY OR VICE VERSA IN BODY. [Friberg, L., Nordberg, 

 G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of 

 Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 

 1986., p. 389] **PEER REVIEWED** 

 Six of 75 workers exposed to 0.05 to 0.1 mg Hg/cu m of mercury vapor in a 

 glass manufacturing plant reported insomnia, and one had tremors. 

 Hyperexcitability was observed in 33 percent of the workers exposed to 

 mercury vapor at concentrations above 0.05 mg Hg/cu m, whereas only 8 

 percent of the workers exposed below this concentration were 

 hyperexcitable. Tremors were observed in 20 percent of the workers in both 

 groups. Occupational mercury exposures resulting in tremors are associated 

 with urinary mercury concentrations ranging from 50 to 200 ug/g 

 creatinine. /Mercury vapor/ [Clayton, G.D., F.E. Clayton (eds.) Patty's 

 Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: 

 Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., 

 p. 2133] **PEER REVIEWED** 

 When 84 mercury exposed workers in a thermometer factory were compared to 

 79 workers not exposed to mercury, the exposed workers were found to have 

 a higher prevalence of static tremor, abnormal Romberg test, and 

 dysdiadochokinesia. There was a correlation between urinary mercury Hg and 

 NAG suggestive of recent mercury toxicity, whereas the CNS signs and 

 symptoms were considered a result of chronic toxicity. No differences 

 existed between the groups of workers with regard to beta-microglobulin 

 and retinol-binding protein, which are considered markers of proximal 

 renal tubule function. [Clayton, G.D., F.E. Clayton (eds.) Patty's 

 Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: 

 Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., 

 p. 2133] **PEER REVIEWED** 

 Forty one male mercury exposed workers were examined for serum 

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 concentration levels of immunoglobulins (IgG, IgA, IgM), 

 alpha-1-antitrypsin (AIAT), alpha-2-macroglobulin (A2M), ceruloplasmin 

 (CPL), and orosomucoid (ORO). In the period preceding this investigation 

 the mercury concentrations in workplace air ranged from 0.106 to 0.783 

 mg/cu m; the range of urinary mercury concentrations was from 0.029 to 

 0.545 mg/l. All but two (IgG and AIAT) of the immune parameters tested 

 were at levels much higher than those found in a control group of 55 

 workers matched by age to the exposed workers and who lived in a 

 relatively clean area. Almost 80% of the workers in the control group 

 demonstrated no value out of the range of normal physiological limits, but 

 only 36.6% of the exposed workers showed normal values. [Clayton, G.D., 

 F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 

 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & 

 Sons Inc., 1993-1994., p. 2136] **PEER REVIEWED** 

MEDICAL SURVEILLANCE: 

 The assessment of mercury exposure can be accomplished through measurement 

 of mercury, which is useful for assessment of recent exposure to any of 

 the three forms of mercury. ... Whole Blood Reference Ranges: Normal - 

 mean level in the general population < 8 ug/l; Exposed - BEI (sampling 

 time at end of shift at end of workweek, measured as total inorganic 

 mercury) 15.0 ug/l. BAT (biological tolerance value for a working 

 material) for metallic and inorganic compounds (sampling time not fixed) 

 50 ug/l; BAT for organic compounds (sampling time not fixed) 100 ug/l. 

 /Mercury/ [Ryan, R.P., C.E. Terry (eds.). Toxicology Desk Reference 4th 

 ed. Volumes 1-3. Taylor & Francis, Washington, D.C. 1997., p. 1577] 

 **PEER REVIEWED** 

 The assessment of mercury exposure can be accomplished through measurement 

 of mercury, which is useful for assessment of recent exposure to any of 

 the three forms of mercury. ... Whole Blood Reference Ranges: Toxic - 0.3 

 ug/100 ml, memory disturbances, impaired eye-hand coordination; 0.5-3 

 ug/100 ml, altered electroencephalograms (EEGs); < 1 - > 10 

 ug/deciliter, increased tremors; 1.4 ug/ ml, decreased immunoglogin G 

 (IgG) and immunoglobin A (IgA) levels; > 1.5 ug/100 ml, disturbances in 

 tests on verbal intelligence and memory; 1-2 ug/100 ml, increased 

 prevalence of abnormal psychomotor scores; 1-2 ug/ 100 ml, increased 

 tremors, impaired eye-hand coordination; > 3 ug/100 ml, (estimated 

 threshold level): increased urinary excretion of beta-galactosidase and 

 high molecular weight proteins. /Mercury/ [Ryan, R.P., C.E. Terry (eds.). 

 Toxicology Desk Reference 4th ed. Volumes 1-3. Taylor & Francis, 

 Washington, D.C. 1997., p. 1577] **PEER REVIEWED** 

 The assessment of mercury exposure can be accomplished through measurement 

 of mercury. However, measurement of mercury in ... /serum or plasma/ is 

 insensitive because mercury is found primarily in the red blood cells. 

 Serum or Plasma Reference Ranges: Normal - not established; Exposed - not 

 established; Toxic - not established. /Mercury/ [Ryan, R.P., C.E. Terry 

 (eds.). Toxicology Desk Reference 4th ed. Volumes 1-3. Taylor & 

 Francis, Washington, D.C. 1997., p. 1578] **PEER REVIEWED** 

 The assessment of mercury exposure can be accomplished through measurement 

 of mercury ... Urine Reference Ranges: Normal - < 20.0 ug/l; Exposed - 

 BEI (sampling time is preshift, measured as total inorganic mercury) 35.0 

 ug/g creatinine; Toxic - 3-53 ug/g creatinine, memory disturbances, 

 impaired eye-hand coordination; 4-53 ug/g creatinine, altered EEGs; 3-272 

 ug/g creatinine, increased anti-laminin antibodies (implicated in the 

 etiology of autoimmune glomerulo-nephritis); 44 ug/g creatinine, decreased 

 Iga and IgG levels; 73 ug/g creatinine, increased static tremors, 

 difficulty with heel-to-toe gait; 50-100 ug/g creatinine, increased 

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 tremors, impaired eye-hand coordination; > 50 ug/g creatinine (estimated 

 threshold level), increased urinary excretion of beta-galactosidase and 

 high molecular weight proteins; 7-1,101 ug/24 hr, abnormal memory tests, 

 decreased tibial nerve velocity, increased median nerve latency in both 

 motor and sensory nerves; 0-510 ug/l, short term memory loss; 5-1,000 

 ug/l, increased tremor frequency and reaction time, impaired eye-hand 

 coordination; < 10- > 1,000 ug/l, increased tremors; 20-450 ug/l, 

 increased motor and sensory nerve latency; > 56 ug/l, disturbances in 

 tests on verbal intelligence and memory; 100-250 ug/l, increased acetyl 

 beta-d-glucosaminidase (NAG) enzyme levels in urine; > 200 ug/l, 

 increased tremors, impaired eye-hand coordination; 300-1,400 ug/l, 

 nephrotic syndrome, albuminuria, hypercholesterolemia; 56 ug/g creatinine, 

 no effect level for proteinuria. /Mercury/ [Ryan, R.P., C.E. Terry (eds.). 

 Toxicology Desk Reference 4th ed. Volumes 1-3. Taylor & Francis, 

 Washington, D.C. 1997., p. 1578] **PEER REVIEWED** 

 Urine Albumin: Albuminuria has been shown to be a specific marker of 

 glomerular dysfunction. Tubular damage, however, can also result in 

 increased levels of albumin in the urine. /Metallic, inorganic and organic 

 mercury/ [Ryan, R.P., C.E. Terry (eds.). Toxicology Desk Reference 4th 

 ed. Volumes 1-3. Taylor & Francis, Washington, D.C. 1997., p. 1580] 

 **PEER REVIEWED** 

 Urinary Beta-2-Microglobulin and/or Retinal Binding Protein: Measurements 

 for the presence of either of these low molecular weight proteins are 

 useful in detection of early impairment of proximal tubular function. 

 However, beta-2-microglobulin is unstable at urinary pH less than 6, and 

 may degrade in the bladder prior to collection and subsequent 

 neutralization of the urine sample. Measurement of retinal binding protein 

 appears to be a better marker for early tubular dysfunction due to its 

 stability in the urine subsequent to collection and analysis. However, 

 retinal binding protein is produced in the liver and not a constitutive 

 protein of the kidney, so that its presence in the kidney provides only 

 indirect evidence of tubular damage. /Metallic, inorganic and organic 

 mercury/ [Ryan, R.P., C.E. Terry (eds.). Toxicology Desk Reference 4th 

 ed. Volumes 1-3. Taylor & Francis, Washington, D.C. 1997., p. 1580] 

 **PEER REVIEWED** 

 Urinary Alpha () and Pi () Isoenzymes of Glutathione S-Transferase: 

 Radio-immunological and Elisa techniques have been developed for 

 quantitation of and isoenzymes of glutathione S-transferase, which are 

 constitutive proteins in the kidney." The isoenzyme is located only in the 

 proximal tubule, while the isoenzyme is located in the distal convoluted 

 tubule, the loop of Henle, and the collecting ducts of the kidney. Damage 

 to epithelial cell membranes can result in the increased excretion of 

 these isoenzymes in the urine. This test for assessing renal tubular 

 damage appears to have many advantages over other available tests, such 

 as: (1) the and isoenzymes are constitutive proteins in the kidney; (2) 

 these isoenzymes are stable in the urine; (3) the test is simple and 

 reproducible; and (4) due to selective localization of the isoenzymes, 

 differential diagnosis of specific tubular damage is possible. In 

 addition, increased levels of these isoenzymes were seen in patients 

 previously exposed to nephrotoxicants where'conventional tests for kidney 

 function were normal, indicating a high degree of sensitivity. /Metallic, 

 inorganic and organic mercury/ [Ryan, R.P., C.E. Terry (eds.). Toxicology 

 Desk Reference 4th ed. Volumes 1-3. Taylor & Francis, Washington, 

 D.C. 1997., p. 1581] **PEER REVIEWED** 

 Urinary Enzyme N-Acetylglucosaminidase: This lysosomal enzyme has shown 

 promise in assessment of subclinical nephrotoxic injury. This enzyme is 

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 not normally filtered at the glomerulus due to its high molecular weight. 

 In the absence of glomerular injury, this enzyme will be detected in the 

 urine as a result of leakage or exocytosis from damaged, stimulated, or 

 exfoliated renal cells. The sensitivity of measurement for this enzyme has 

 not been thoroughly studied, but it's usefulness has shown some promise. 

 However, this enzyme is unstable at urinary pH greater than 8, which could 

 diminish the sensitivity of the measurement due to enzyme degradation. 

 /Metallic, inorganic and organic mercury/ [Ryan, R.P., C.E. Terry (eds.). 

 Toxicology Desk Reference 4th ed. Volumes 1-3. Taylor & Francis, 

 Washington, D.C. 1997., p. 1581] **PEER REVIEWED** 

 Routine Urinalysis: Performing a routine urinalysis including parameters 

 such as specific gravity, glucose, and microscopic examination may be 

 useful for assessing renal toxicity. /Metallic, inorganic and organic 

 mercury/ [Ryan, R.P., C.E. Terry (eds.). Toxicology Desk Reference 4th 

 ed. Volumes 1-3. Taylor & Francis, Washington, D.C. 1997., p. 1581] 

 **PEER REVIEWED** 

 Evaluation of Peripheral Neuropathy: Nerve conduction study; 

 Electromyography; Quantitative sensory testing; Thermography. /Metallic, 

 inorganic and organic mercury/ [Ryan, R.P., C.E. Terry (eds.). Toxicology 

 Desk Reference 4th ed. Volumes 1-3. Taylor & Francis, Washington, 

 D.C. 1997., p. 1584] **PEER REVIEWED** 

 Evaluation of Central Nervous System Effects: Evaluation of CNS effects 

 can be performed through neuropsychological assessment, which consists of 

 a clinical interview and administration of standardized personality and 

 neuropsychological tests. The areas that the neuropsychology test 

 batteries focus on include the domains of memory and attention; 

 visuoperceptual, visual scanning, visuospatial, and visual memory; and 

 motor speed and reaction time. There is limited data on which components 

 of the test batteries are best indicators of early CNS effects. /Metallic, 

 inorganic and organic mercury/ [Ryan, R.P., C.E. Terry (eds.). Toxicology 

 Desk Reference 4th ed. Volumes 1-3. Taylor & Francis, Washington, 

 D.C. 1997., p. 1584] **PEER REVIEWED** 

 Evaluation of Cranial Neuropathies: Evaluation of cranial nerve damage, as 

 evidenced by symptoms such as loss of balance, visual function, smell, 

 taste, or sensation on the face, can be accomplished through a physical 

 examination focusing on tests such as: Smell Assessment ... Visual 

 Assessment ... Facial and Trigeminal Nerve Assessment ... Vestibular 

 Assessment ... Hearing Assessment. /Metallic, inorganic and organic 

 mercury/ [Ryan, R.P., C.E. Terry (eds.). Toxicology Desk Reference 4th 

 ed. Volumes 1-3. Taylor & Francis, Washington, D.C. 1997., p. 1584] 

 **PEER REVIEWED** 

 Liver Function Tests: Biochemical tests - Enzymes that reflect 

 cholestasis: alkaline phosphatase (AP), 5'-nucleotidase (5'-NT) and 

 leucine aminopeptidase (LAP); Enzymes that detect direct hepatic damage: 

 aspartate aminotransferase (AST) and alanine aminotransferase (ALT). 

 Clearance tests - indocyanine green, antipyrine test and serum bile acids. 

 [Ryan, R.P., C.E. Terry (eds.). Toxicology Desk Reference 4th ed. Volumes 

 1-3. Taylor & Francis, Washington, D.C. 1997., p. 1582] **PEER 

 REVIEWED** 

 Complete Blood Count: Mercury has been shown to cause hematological 

 changes, which can be assessed by performing a complete blood count. 

 [Ryan, R.P., C.E. Terry (eds.). Toxicology Desk Reference 4th ed. Volumes 

 1-3. Taylor & Francis, Washington, D.C. 1997., p. 1580] **PEER 

 REVIEWED** 

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 Respiratory Symptom Questionnaires: Questionnaires have been published by 

 the American Thoracic Society and the British Medical Research Council. 

 These questionnaires have been found to be useful in identification of 

 people with chronic bronchitis, however certain pulmonary function tests 

 such as FEV1 have been found to be better predictors of chronic airflow 

 obstruction. [Ryan, R.P., C.E. Terry (eds.). Toxicology Desk Reference 4th 

 ed. Volumes 1-3. Taylor & Francis, Washington, D.C. 1997., p. 1583] 

 **PEER REVIEWED** 

 Chest Radiography: This test is widely used for assessing pulmonary 

 disease. Chest radiographs have been found to be useful for detection of 

 early lung cancer in asymptomatic people, especially for detection of 

 peripheral tumors such as adenocarcinomas. However, even though OSHA 

 mandates this test for exposure to some toxicants such as asbestos, there 

 are conflicting views on its efficacy in detection of pulmonary disease. 

 [Ryan, R.P., C.E. Terry (eds.). Toxicology Desk Reference 4th ed. Volumes 

 1-3. Taylor & Francis, Washington, D.C. 1997., p. 1583] **PEER 

 REVIEWED** 

 Pulmonary Function Tests: The tests that have been found to be practical 

 for population monitoring include: Spirometry and expiratory flow-volume 

 curves; Determination of lung volumes; Diffusing capacity for carbon 

 monoxide; Single-breath nitrogen washout; Inhalation challenge tests; 

 Serial measurements of peak expiratory flow; Exercise testing. [Ryan, 

 R.P., C.E. Terry (eds.). Toxicology Desk Reference 4th ed. Volumes 1-3. 

 Taylor & Francis, Washington, D.C. 1997., p. 1583] **PEER REVIEWED** 

 Sputum Cytology: Sputum cytology along with chest radiographs have been 

 the standard procedures for detecting early lung cancer in asymptomatic 

 patients. Sputum cytology has been found to be useful for detection of 

 central tumors, especially squamous carcinomas. [Ryan, R.P., C.E. Terry 

 (eds.). Toxicology Desk Reference 4th ed. Volumes 1-3. Taylor & 

 Francis, Washington, D.C. 1997., p. 1583] **PEER REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 ONE OF MAJOR SOURCES OF ... EXPOSURE IS IN CHLOR-ALKALI PLANTS ... /OTHER 

 SOURCES ARE/ MINING & REFINING OF MERCURY ... FROM PROCESSING OF 

 CINNABAR (HGS) ... MFR & USE OF LIQ HG-CONTAINING INSTRUMENTS ... AN 

 OFTEN UNREALIZED SOURCE OF EXPOSURE THROUGH BREAKAGE, SPILLAGE, OR 

 CARELESS HANDLING. [Clayton, G. D. and F. E. Clayton (eds.). Patty's 

 Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. 

 New York: John Wiley Sons, 1981-1982., p. 1770] **PEER REVIEWED** 

 ... MOTHERS EXPOSED TO ELEMENTAL MERCURY THROUGH THEIR DENTAL WORK PLACE 

 ... /SHOWED/ SIGNIFICANTLY INCREASED MERCURY CONTENT IN THEIR BABIES' 

 PLACENTA & MEMBRANES. ... EXPOSURE LIMITS FOR WOMEN OF CHILDBEARING 

 AGE & LEVELS AT WHICH TOXICITY MIGHT BE EXPECTED /HAVE BEEN 

 SUGGESTED/. FOR FETUS & NEWBORN, THE TOXIC LEVEL IS GIVEN AS 3 UG 

 HG/G. [Shepard, T.H. Catalog of Teratogenic Agents. 4th ed. Baltimore, MD: 

 Johns Hopkins University Press, 1983., p. 278] **PEER REVIEWED** 

 INHALATION OF VAPOR BY LABORATORY WORKERS IN CLOSED SPACE LED TO BRONCHIAL 

 IRRITATION /& CHARACTERISTIC MERCURY POISONING SYMPTOMS/ ... CHRONIC 

 MERCURIALISM IN FUR-CUTTING & FELT-HAT INDUSTRIES /IS REPORTED/. 

 ALTHOUGH MERCURIC NITRATE WAS MATERIAL USED TO TREAT FUR FROM WHICH FELT 

 WAS MADE, MERCURY WAS GRADUALLY RELEASED FROM FUR & FELT IN FORM OF 

 METALLIC MERCURY VAPOR. ... THE WORKERS HAD MIXED EXPOSURE TO DUST OF 

 MERCURY CMPD (ESP THE NITRATE) & TO VAPOR OF ELEMENT. ... POISONING 

 WAS SIMILAR TO THAT OBSERVED ... /WITH/ METALLIC MERCURY ONLY. [Hayes, 

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 Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and 

 Wilkins, 1982., p. 12] **PEER REVIEWED** 

 NIOSH, IN ITS CRITERIA DOCUMENT ... CONCLUDED THAT THE STD SHOULD BE AT 

 LEAST AS LOW AS 0.05 MG/CU M ... /BECAUSE/ ERETHISM, RATHER THAN TREMOR, 

 MAY BE THE MOST CHARACTERISTIC SYMPTOM OF CHRONIC MERCURIALISM /OCCURRING 

 IN 33% OF WORKERS ABOVE 0.05 MG/CU M & IN 8% OF WORKERS BELOW THIS 

 LEVEL/. ... /STUDIES OF WORKPLACES REVEAL/ THAT MUCH HIGHER EXPOSURES TO 

 MERCURY VAPOR ... /OCCUR WHEN MEASURED/ BY PERSONAL SAMPLING DEVICES 

 (0.016 TO 0.687 MG/CU M). THESE DIFFERENCES HAVE BEEN ATTRIBUTABLE TO 

 MERCURY CONTAMINATION OF CLOTHING, WHICH MAY CAUSE SIGNIFICANT EXPOSURE 

 AFTER WORK HOURS. [American Conference of Governmental Industrial 

 Hygienists. Documentation of the Threshold Limit Values and Biological 

 Exposure Indices. 5th ed. Cincinnati, OH: American Conference of 

 Governmental Industrial Hygienists, 1986., p. 358] **PEER REVIEWED** 

 Acute poisoning is major threat in home & on farm, but, because 

 mercury is a cumulative poison, subacute & chronic intoxications are 

 recognized, particularly in industry. [Gosselin, R.E., R.P. Smith, H.C. 

 Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: 

 Williams and Wilkins, 1984., p. III-262] **PEER REVIEWED** 

 Prior to 1991, phenylmercuric compounds were used as biocides in 25-30% of 

 interior and exterior latex paint; however, this use of mercury was 

 voluntarily discontinued for interior paint in 1990 and for exterior paint 

 in 1991(1). The use of phenylmercury resulted in the exposure of house 

 painters and residents to mercury vapors in the homes where interior and 

 exterior latex paint was applied(1). Although the use of mercury biocides 

 in latex paint has been discontinued, it is possible that people who use 

 old latex paint in their homes will be exposed to mercury for a 

 considerable time(1). Furthermore, although phenylmercury use in exterior 

 latex paints was discontinued in 1991, paint companies were allowed to 

 continue to produce and sell paint containing phenylmercury until the 

 existing stocks of phenylmercury were exhausted(1). [(1) ATSDR; 

 Toxicological Profile for Mercury p. 312. Research Triangle Institute 

 205-93-0606 (1998)] **PEER REVIEWED** 

AVERAGE DAILY INTAKE: 

 Assuming an ambient air level of 50 ng/cu m, the average daily intake of 

 metallic mercury vapor would amount to 1 ug/day due to inhalation. ... The 

 average daily intake of those sub-groups of the general population living 

 in specially polluted areas is difficult to estimate with any accuracy. 

 ... Daily intake from occupational exposure is almost impossible to 

 estimate because of the wide variation in exposure conditions in industry. 

 [WHO; Environ Health Criteria: Mercury p.64 (1976)] **PEER REVIEWED** 

TOXICITY SUMMARY: 

 IDENTIFICATION: In its elemental form, mercury is a heavy silvery liquid 

 at room temperature and has a very high vapour pressure. Mercury vapor is 

 more soluble in plasma, whole blood, and hemoglobin than in distilled 

 water, where it dissolves only slightly. The major natural sources of 

 mercury are degassing of the earth's crust, emissions from volcanoes, and 

 evaporation from natural bodies of water. (The world-wide mining of 

 mercury is estimated to yield about 10,000 tons per year. The activities 

 lead to some losses of mercury and direct discharges to the atmosphere). 

 Other important sources are fossil fuel combustion, metal sulfide ore 

 smelting, gold refining, cement production, refuse incineration, and 

 industrial applications of metals. A major use of mercury is as a cathode 

 in the electrolysis of sodium chloride. Mercury is used in the electrical 

 industry, in control instruments in the home and industry, and in 

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 laboratory and medical instruments. A very large amount of mercury is used 

 for the extraction of gold. Dental silver amalgam for tooth filling 

 contains large amounts of mercury. Use of skin-lightening soap and creams 

 can give rise to substantial mercury exposure. Occupational exposure to 

 inorganic mercury has been investigated in chloralkali plants, mercury 

 mines, thermometer factories, refineries, and in dental clinics. High 

 mercury levels have been reported for all these occupational exposure 

 situations, although levels vary according to work environment conditions. 

 HUMAN EXPOSURE: The general population is primarily exposed to mercury 

 through the diet and dental amalgam. Acute inhalation exposure to mercury 

 vapor may be followed by chest pains, dyspnea, coughing, hemoptysis, and 

 sometimes interstitial pneumonitis leading to death. (The ingestion of 

 mercuric compounds, in particular mercuric chloride, has caused ulcerative 

 gastroenteritis and acute tubular necrosis causing death from anuria where 

 dialysis was not available). The central nervous system is the critical 

 organ for mercury vapor exposure. Subacute exposure has given rise to 

 psychotic reactions characterized by delerium, hallucinations, and 

 suicidal tendency. Occupational exposure has resulted in erethism as the 

 principal feature of a broad ranging functional disturbance. The kidney is 

 the critical organ following the ingestion of inorganic divalent mercury 

 salts. Occupational exposure to metallic mercury has long been associated 

 with the development of proteinuria. Both metallic mercury vapor and 

 mercury compounds have given rise to contact dermatitis. Mercurial 

 pharmaceuticals have been responsible for Pink disease (acrodynia) in 

 children, and mercury vapor exposure may be a cause of "Kawasaki" disease. 

 Results of both human and animal studies indicate that about 80% of 

 inhaled metallic mercury vapour is retained by the body, whereas liquid 

 metallic mercury is poorly absorbed via the gastrointestinal tract. ANIMAL 

 STUDIES: Evidence of damage to brain, kidney, heart, and lungs have been 

 reported in rabbits exposed acutely to metallic mercury vapor at certain 

 concentrations. Both reversible and irreversible toxic effects may be 

 caused by mercury and its compounds. In two studies, tremor and 

 behavioural effects were observed in rabbits and rats after several weeks 

 of exposure to metallic mercury vapour. Depending upon the animal strain 

 tested, either auto-immunity or immunosuppression is observed. The most 

 sensitive adverse effect caused by mercuric mercury is the formation of 

 mercuric-mercury-induced auto-immune glomerulonephritis. Mercuric chloride 

 was found to induce gene mutations in mouse lymphoma cells and DNA damage 

 in rat and mouse fibroblasts. The World Health Organization reported no 

 evidence that inorganic mercury is carcinogenic. The neurotoxic effect 

 seen after exposure to metallic mercury vapour is attributable to the 

 divalent mercury ion formed through oxidation in the brain tissue. 

 Significantly more mercury is transported to the brain of mice and monkeys 

 after the inhalation of elemental mercury than after the intravenous 

 injection of equivalent doses of the mercuric form. [World Health 

 Organization/International Programme on Chemical Safety. Environmental 

 Health Criteria 118 Inorganic Mercury. pp. 13-21, 68-83 (1991)] **PEER 

 REVIEWED** 

EVIDENCE FOR CARCINOGENICITY: 

 CLASSIFICATION: D; not classifiable as to human carcinogenicity. BASIS FOR 

 CLASSIFICATION: Based on inadequate human and animal data. Epidemiologic 

 studies failed to show a correlation between exposure to elemental mercury 

 vapor and carcinogenicity; the findings in these studies were confounded 

 by possible or known concurrent exposures to other chemicals, including 

 human carcinogens, as well as lifestyle factors (e.g., smoking). Findings 

 from genotoxicity tests are severely limited and provide equivocal 

 evidence that mercury adversely affects the number or structure of 

 chromosomes in human somatic cells. HUMAN CARCINOGENICITY DATA: 

 Inadequate. ANIMAL CARCINOGENICITY DATA: Inadequate. [U.S. Environmental 

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 Protection Agency's Integrated Risk Information System (IRIS) on Mercury 

 (Inorganic ) (7439-97-6) Available from: http://www.epa.gov/ngispgm3/iris 

 on the Substance File List as of March 15, 2000] **PEER REVIEWED** 

 Evaluation: There is inadequate evidence in humans for the carcinogenicity 

 of mercury and mercury compounds. There is inadequate evidence in 

 experimental animals for the carcinogenicity of metallic mercury. There is 

 limited evidence in experimental animals for the carcinogenicity of 

 mercuric chloride. There is sufficient evidence in experimental animals 

 for the carcinogenicity of methylmercury chloride. In making the overall 

 evaluation, the Working Group took into account evidence that 

 methylmercury compounds are similar with regard to absorption, 

 distribution, metabolism, excretion, genotoxicity and other forms of 

 toxicity. Overall evaluation: Methylmercury compounds are possibly 

 carcinogenic to humans (Group 2B). Metallic mercury and inorganic mercury 

 compounds are not classifiable as to their carcinogenicity to humans. 

 (Group 3). /Mercury and mercury compounds/ [IARC. Monographs on the 

 Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World 

 Health Organization, International Agency for Research on Cancer, 

 1972-PRESENT. (Multivolume work)., p. V58 324 (1993)] **PEER REVIEWED** 

 A4: Not classifiable as a human carcinogen. /Mercury, elemental and 

 inorganic forms, as Hg/ [American Conference of Governmental Industrial 

 Hygienists TLVs and BEIs. Threshold Limit Values for Chemical Substances 

 and Physical Agents and Biological Exposure Indices. Cincinnati, OH, 2008, 

 p. 37] **QC REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 ONE OF MAJOR SOURCES OF ... EXPOSURE IS IN CHLOR-ALKALI PLANTS ... /OTHER 

 SOURCES ARE/ MINING & REFINING OF MERCURY ... FROM PROCESSING OF 

 CINNABAR (HGS) ... MFR & USE OF LIQ HG-CONTAINING INSTRUMENTS ... AN 

 OFTEN UNREALIZED SOURCE OF EXPOSURE THROUGH BREAKAGE, SPILLAGE, OR 

 CARELESS HANDLING. [Clayton, G. D. and F. E. Clayton (eds.). Patty's 

 Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. 

 New York: John Wiley Sons, 1981-1982., p. 1770] **PEER REVIEWED** 

 ... MOTHERS EXPOSED TO ELEMENTAL MERCURY THROUGH THEIR DENTAL WORK PLACE 

 ... /SHOWED/ SIGNIFICANTLY INCREASED MERCURY CONTENT IN THEIR BABIES' 

 PLACENTA & MEMBRANES. ... EXPOSURE LIMITS FOR WOMEN OF CHILDBEARING 

 AGE & LEVELS AT WHICH TOXICITY MIGHT BE EXPECTED /HAVE BEEN 

 SUGGESTED/. FOR FETUS & NEWBORN, THE TOXIC LEVEL IS GIVEN AS 3 UG 

 HG/G. [Shepard, T.H. Catalog of Teratogenic Agents. 4th ed. Baltimore, MD: 

 Johns Hopkins University Press, 1983., p. 278] **PEER REVIEWED** 

 INHALATION OF VAPOR BY LABORATORY WORKERS IN CLOSED SPACE LED TO BRONCHIAL 

 IRRITATION /& CHARACTERISTIC MERCURY POISONING SYMPTOMS/ ... CHRONIC 

 MERCURIALISM IN FUR-CUTTING & FELT-HAT INDUSTRIES /IS REPORTED/. 

 ALTHOUGH MERCURIC NITRATE WAS MATERIAL USED TO TREAT FUR FROM WHICH FELT 

 WAS MADE, MERCURY WAS GRADUALLY RELEASED FROM FUR & FELT IN FORM OF 

 METALLIC MERCURY VAPOR. ... THE WORKERS HAD MIXED EXPOSURE TO DUST OF 

 MERCURY CMPD (ESP THE NITRATE) & TO VAPOR OF ELEMENT. ... POISONING 

 WAS SIMILAR TO THAT OBSERVED ... /WITH/ METALLIC MERCURY ONLY. [Hayes, 

 Wayland J., Jr. Pesticides Studied in Man. Baltimore/London: Williams and 

 Wilkins, 1982., p. 12] **PEER REVIEWED** 

 NIOSH, IN ITS CRITERIA DOCUMENT ... CONCLUDED THAT THE STD SHOULD BE AT 

 LEAST AS LOW AS 0.05 MG/CU M ... /BECAUSE/ ERETHISM, RATHER THAN TREMOR, 

 MAY BE THE MOST CHARACTERISTIC SYMPTOM OF CHRONIC MERCURIALISM /OCCURRING 

 IN 33% OF WORKERS ABOVE 0.05 MG/CU M & IN 8% OF WORKERS BELOW THIS 

 LEVEL/. ... /STUDIES OF WORKPLACES REVEAL/ THAT MUCH HIGHER EXPOSURES TO 

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 MERCURY VAPOR ... /OCCUR WHEN MEASURED/ BY PERSONAL SAMPLING DEVICES 

 (0.016 TO 0.687 MG/CU M). THESE DIFFERENCES HAVE BEEN ATTRIBUTABLE TO 

 MERCURY CONTAMINATION OF CLOTHING, WHICH MAY CAUSE SIGNIFICANT EXPOSURE 

 AFTER WORK HOURS. [American Conference of Governmental Industrial 

 Hygienists. Documentation of the Threshold Limit Values and Biological 

 Exposure Indices. 5th ed. Cincinnati, OH: American Conference of 

 Governmental Industrial Hygienists, 1986., p. 358] **PEER REVIEWED** 

 Acute poisoning is major threat in home & on farm, but, because 

 mercury is a cumulative poison, subacute & chronic intoxications are 

 recognized, particularly in industry. [Gosselin, R.E., R.P. Smith, H.C. 

 Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: 

 Williams and Wilkins, 1984., p. III-262] **PEER REVIEWED** 

 Prior to 1991, phenylmercuric compounds were used as biocides in 25-30% of 

 interior and exterior latex paint; however, this use of mercury was 

 voluntarily discontinued for interior paint in 1990 and for exterior paint 

 in 1991(1). The use of phenylmercury resulted in the exposure of house 

 painters and residents to mercury vapors in the homes where interior and 

 exterior latex paint was applied(1). Although the use of mercury biocides 

 in latex paint has been discontinued, it is possible that people who use 

 old latex paint in their homes will be exposed to mercury for a 

 considerable time(1). Furthermore, although phenylmercury use in exterior 

 latex paints was discontinued in 1991, paint companies were allowed to 

 continue to produce and sell paint containing phenylmercury until the 

 existing stocks of phenylmercury were exhausted(1). [(1) ATSDR; 

 Toxicological Profile for Mercury p. 312. Research Triangle Institute 

 205-93-0606 (1998)] **PEER REVIEWED** 

AVERAGE DAILY INTAKE: 

 Assuming an ambient air level of 50 ng/cu m, the average daily intake of 

 metallic mercury vapor would amount to 1 ug/day due to inhalation. ... The 

 average daily intake of those sub-groups of the general population living 

 in specially polluted areas is difficult to estimate with any accuracy. 

 ... Daily intake from occupational exposure is almost impossible to 

 estimate because of the wide variation in exposure conditions in industry. 

 [WHO; Environ Health Criteria: Mercury p.64 (1976)] **PEER REVIEWED** 

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The following information was generated from the 

Hazardous Substances Data Bank (HSDB), 

a database of the National Library of Medicine's TOXNET system 

(http://toxnet.nlm.nih.gov) on October 27, 2009. 

Query: The chemical name molybdenum was identified. 

The following terms were added from ChemIDplus: 

mchvl 

CAS Registry Number: 7439-98-7 

1 

NAME: MOLYBDENUM 

RN: 7439-98-7 

NOTE: 

 This record contains information for molybdenum in its zero valence state 

 only. For general toxicity and environmental fate of molybdenum ions and 

 molybdenum compounds, refer to the MOLYBDENUM COMPOUNDS record; for 

 compound specific information, refer to the appropriate individual 

 records, e.g., molybdenum trioxide, etc. For information on the 

 radiological aspects of molybdenum and its compounds, refer to the 

 MOLYBDENUM, RADIOACTIVE record. For general toxicological, safety and 

 handling, and environmental information on ionizing radiation emitted from 

 chemical sources including molybdenum, refer to the IONIZING RADIATION 

 RECORD. 

HUMAN HEALTH EFFECTS: 

HUMAN TOXICITY EXCERPTS: 

 /SIGNS AND SYMPTOMS/ Metallic and poorly soluble molybdenum compounds 

 (such as molybdenum disulfide, molybdenum dioxide) have limited animal 

 experimental data and no human toxicity data. From the scant information 

 available, these materials thought to be poorly soluble and to have low 

 animal and human toxicity. Until toxicologic or human data indicate a more 

 serious threat to human health, these materials are assigned TLV–TWAs of 

 10 mg/m3 (inhalable particulate mass) and 3 mg/m3 (respirable particulate 

 mass) to protect against any irritant effects of these materials. 

 /Metallic molybdenum and poorly soluble molybdenum/ [American Conference 

 of Governmental Industrial Hygienists. Documentation of the TLV's and 

 BEI's with Other World Wide Occupational Exposure Values. CD-ROM 

 Cincinnati, OH 45240-1634 2004.] **PEER REVIEWED** 

 /SIGNS AND SYMPTOMS/ Pneumoconiosis with X-ray findings and subjective 

 symptoms ... reported in 3 out of 19 workers exposed to metallic 

 molybdenum and molybdenum trioxide. Exposure varied between 1 and 19 mg/cu 

 m for 4 to 7 yr. /Metallic molybdenum and molybdenum trioxide/ [Friberg, 

 L., Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the 

 Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science 

 Publishers B.V., 1986., p. V2 452] **PEER REVIEWED** 

 /SIGNS AND SYMPTOMS/ Increased blood uric acid values and gout-like 

 symptoms have been reported among workers exposed to molybdenum in a 

 copper-molybdenum plant ... . /Molybdenum and compounds/ [Friberg, L., 

 Nordberg, G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the 

 Toxicology of Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science 

 Publishers B.V., 1986., p. V2 446] **PEER REVIEWED** 

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 /SIGNS AND SYMPTOMS/ In a 1984 review, an increased incidence of 

 nonspecific symptoms, including weakness, fatigue, headache, anorexia, and 

 joint and muscle pains, was reported among mining and metallurgy workers 

 exposed at 60 to 600 mg/cu m molybdenum /Molybdenum dusts/ [American 

 Conference of Governmental Industrial Hygienists. Documentation of the 

 TLV's and BEI's with Other World Wide Occupational Exposure Values. CD-ROM 

 Cincinnati, OH 45240-1634 2004.] **PEER REVIEWED** 

 /CASE REPORTS/ A 44-year-old woman was exposed to metallic molybdenum and 

 molybdenum trioxide dust at 1 to 3 mg/cu m with occasional excursions 

 > /= 25 mg/cu m molybdenum trioxide for 5 years. She complained of 

 difficulty in breathing, general weakness, and dizziness. /Metallic 

 molybdenum and molybdenum trioxide/ [American Conference of Governmental 

 Industrial Hygienists. Documentation of the TLV's and BEI's with Other 

 World Wide Occupational Exposure Values. CD-ROM Cincinnati, OH 45240-1634 

 2004.] **PEER REVIEWED** 

 /EPIDEMIOLOGY STUDIES/ Human data on molybdenum and cancer were lacking 

 until a study ... was published in 1999. In a case-control study of lung 

 cancer and occupational exposures, patients were enrolled from ten 

 hospitals in the Antwerp region of Belgium. The cases (n = 478) were all 

 incident male patients with histologically confirmed lung cancer, and 

 controls (n = 536) were recruited from all male patients without cancer or 

 primary lung disease admitted in the corresponding week to the same 

 hospital. Information was obtained on smoking, work history, marital 

 status, education, and socioeconomic status from interviewer-administered 

 questionnaires. Occupational exposures to 16 suspected carcinogens were 

 sought through specific questions of the study subjects (self-reported 

 exposures), or by obtaining information about their job history and 

 constructing a job-task exposure matrix (JTEM) with the assistance of 

 occupational health specialists. The control workers were of similar age 

 to the cases but had substantially fewer smokers, were more likely to be 

 married, were slightly better educated and of higher socioeconomic status. 

 As expected, strong associations were found between lung cancer and 

 smoking: ex-smokers had an odds ratio of 4.2 (95% confidence interval 

 (CI), 1.8 to 9.8), and current smokers had an odds ratio of 14.5 (95% CI, 

 6.3 to 33.4), relative to nonsmokers. The relationships between lung 

 cancer and occupational exposures were assessed using logistic regression 

 models that included variables for age, smoking, marital status, and 

 socioeconomic status. Self-reported exposures produced adjusted odds 

 ratios greater than 2.0 for chromium and arsenic, but these were not 

 significant. Using exposures derived from the JTEM, many more workers were 

 identified who were potentially exposed to the 16 suspected carcinogens. 

 The JTEM data therefore increased the power of the study to detect 

 associations between lung cancer and exposures. Associations with lung 

 cancer were statistically significant for those ever exposed to molybdenum 

 (odds ratio, 2.1; 95 % CI, 1.2 to 3.7), chromium (odds ratio, 1.4; 95% CI, 

 1.0 to 1.9), or mineral oils (odds ratio, 1.7; 95% CI, 1.1 to 2.7). 

 Nonsignificant odds ratios of 1.0 to 1.5 were found for other potential 

 carcinogens (including arsenic, nickel, bis-chloromethyl ether, 

 polyaromatic hydrocarbons, wood dust, and asbestos). ... No industrial 

 hygiene measurements for the 16 potential carcinogens under study /were 

 reported. The duration of working in particular jobs was obtained from 

 questionnaires and linked to the JTEM to derive periods of exposure to 

 particular agents. A positive relationship between lung cancer and working 

 with molybdenum compounds for greater than 21 years was observed ... . No 

 relationship was found for lung cancer and the duration of exposure to 

 chromium or mineral oils, the latter showing an inverse relationship with 

 duration of exposure. Molybdenum exposures were correlated with chromium 

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 and mineral oil exposures for many job categories, but only molybdenum 

 showed an exposure–response pattern consistent with being a lung 

 carcinogen ... . Because the association with lung cancer was much 

 stronger for molybdenum than for other potential carcinogens, it seems 

 unlikely that the association of lung cancer with molybdenum could be 

 attributed instead to chromium, mineral oils, or another occupational 

 agent. /Molybdenum dusts/ [American Conference of Governmental Industrial 

 Hygienists. Documentation of the TLV's and BEI's with Other World Wide 

 Occupational Exposure Values. CD-ROM Cincinnati, OH 45240-1634 2004.] 

 **PEER REVIEWED** 

 /OTHER TOXICITY INFORMATION/ ... Molybdenum compounds exhibit a low order 

 of toxicity, but ... some differences in toxicity may be ascribed to 

 different compounds; the trioxide and ammonium molybdate were more toxic 

 than the ore molybdenite, the metal or the dioxide. /Molybdenum metal/ 

 [American Conference of Governmental Industrial Hygienists. Documentation 

 of the Threshold Limit Values and Biological Exposure Indices. 5th ed. 

 Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 

 1986., p. 415] **PEER REVIEWED** 

SKIN, EYE AND RESPIRATORY IRRITATIONS: 

 Contact irritates the skin and eyes. Inhalation can irritate the 

 respiratory tract ... [Sittig, M. Handbook of Toxic and Hazardous 

 Chemicals and Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes 

 Publications, 2002., p. 1634] **PEER REVIEWED** 

 Fume from arcing molybdenum metal causes respiratory irritation in 

 animals. [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. 

 (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. 

 DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. 

 Government Printing Office, Jan. 1981., p. 2] **PEER REVIEWED** 

MEDICAL SURVEILLANCE: 

 The following medical procedures should be made available to each employee 

 who is exposed to molybdenum and insoluble molybdenum compounds at 

 potentially hazardous levels: Initial medical screening: Employees should 

 be screened for history of certain medical conditions /kidney disease; 

 chronic respiratory disease; liver disease/ which might place the employee 

 at increased risk from molybdenum and insoluble molybdenum compounds 

 exposure. Periodic medical exam: Any employee developing the above listed 

 conditions should be referred for further medical examination. /Molybdenum 

 and insoluble molybdenum compounds/ [Mackison, F. W., R. S. Stricoff, and 

 L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines 

 for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). 

 Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1] **PEER 

 REVIEWED** 

POPULATIONS AT SPECIAL RISK: 

 In persons with impaired pulmonary function, especially those with 

 obstructive airway diseases, the breathing of insoluble molybdenum 

 compounds might cause exacerbation of symptoms due to their irritant 

 properties. /Molybdenum and insoluble molybdenum compounds/ [Mackison, F. 

 W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - 

 Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) 

 Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing 

 Office, Jan. 1981., p. 2] **PEER REVIEWED** 

SKIN, EYE AND RESPIRATORY IRRITATIONS: 

 Contact irritates the skin and eyes. Inhalation can irritate the 

 respiratory tract ... [Sittig, M. Handbook of Toxic and Hazardous 

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 Chemicals and Carcinogens, 2002. 4th ed.Vol 1 A-H Norwich, NY: Noyes 

 Publications, 2002., p. 1634] **PEER REVIEWED** 

 Fume from arcing molybdenum metal causes respiratory irritation in 

 animals. [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. 

 (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. 

 DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. 

 Government Printing Office, Jan. 1981., p. 2] **PEER REVIEWED** 

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The following information was generated from the 

Hazardous Substances Data Bank (HSDB), 

a database of the National Library of Medicine's TOXNET system 

(http://toxnet.nlm.nih.gov) on October 27, 2009. 

Query: The chemical name nickel was identified. 

The following terms were added from ChemIDplus: 

raney nickel 

raney alloy 

nickel sponge 

nichel 

CAS Registry Number: 7440-02-0 

1 

NAME: NICKEL, ELEMENTAL 

RN: 7440-02-0 

NOTE: 

 This record contains information for nickel in its zero valence state 

 only. For general toxicology and environmental fate of nickel ion and 

 nickel compounds, refer to the NICKEL COMPOUNDS record; for 

 compound-specific information, refer to the appropriate individual 

 records, e.g., nickel sulfate, nickel chloride, etc. 

HUMAN HEALTH EFFECTS: 

TOXICITY SUMMARY: 

 Nickel is a ubiquitous trace metal and occurs in soil, water, air and the 

 biosphere. Nickel ore deposits are accumulations of nickel sulfide 

 minerals (mostly pentlandite) and laterites. Most nickel is used for 

 production of stainless steel and other nickel alloys with high corrosion 

 and temperature resistance. Nickel levels in terrestrial and aquatic 

 organisms can vary over several orders of magnitude. Dermal exposure in 

 the general environment is important for the induction and maintenance of 

 contact hypersensitivity caused by daily contact with nickel plated 

 objects or nickel containing alloys (e.g. jewellery, coins or clips). 

 Iatrogenic exposure to nickel results from implants and prostheses made 

 from nickel containing alloys, from iv or dialysis fluids and from 

 radiographic contrast media. In the working environment, airborne nickel 

 concentrations can vary from a few microgram/cu m to a few mg/cu m, 

 depending upon the process involved and the nickel content of the material 

 being handled. Workers are exposed to nickel containing dusts and fumes 

 during welding, plating, grinding, mining, nickel refining, and in steel 

 plants. Dermal exposure to nickel may occur in a wide range of jobs, 

 either by direct exposure, dissolved nickel in refining, electroplating 

 and electroforming industries or by handling nickel containing materials. 

 Nickel can be absorbed in human beings and animals via inhalation or 

 ingestion or percutaneously. Respiratory absorption with secondary 

 gastrointestinal absorption (insoluble and soluble) is a major route of 

 entry during occupational exposure. Percutaneous absorption is negligible, 

 quantatively, but is important in the pathogenesis of contact 

 hypersensitivity. Nickel is transported in the blood, principally bound to 

 albumin. Gastrointestinal absorption of nickel is variable and depends on 

 the composition of the diet. All body secretions are potential routes of 

 excretion including the urine, bile, sweat, tears, milk and mucociliary 

 fluid. Non-absorbed nicke is eliminated in the feces. Data on nickel 

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 excretion suggest a two compartment model. Nickel concentration in the 

 serum and urine of healthy non-occupationally exposed adults are 0.2 ug/l 

 (range: 0.05-1.1 ug/l) and 1.5 ug creatinine (range: 0.5-4.0 mg/g 

 creatinine, respectively. The body burden of nickel in non-exposed 70 kg 

 adult is 0.5 ug. Nickel is essential for the catalytic activity of some 

 plant and bacterial enzymes. Slow weight gain, anemia and decreased 

 viability has been described in some animal species after dietary 

 deprivation of nickel. Contact allergy to nickel is very common in human 

 beings; experimental sensitization in animals is only successful under 

 special conditions. Longterm inhalation exposure to metallic nickel caused 

 mucosal damage and inflammatory reaction, sometimes accompanied by slight 

 fibrosis, was observed in rabbits after high level exposure to nickel 

 graphite dust. Metallic nickel induced local mesenchymal tumors in a 

 variety of experimental animals after im, sc, intraosseous, intrarenal, 

 intra-articular, pleural, intraocular, intratesticular or intra-adipose 

 administrtation. Metallic nickel has been tested for carcinogenicity by 

 parenteral routes of administration, local tumors were noted. In studies 

 using repeated intratracheal instillation, nickel powder caused 

 respiratory tumors. Chronic effects such as rhinitis, sinusitis, nasal 

 septal perforations and asthma have been reported in nickel refinery and 

 nickel plating workers. Some researchers reported pulmonary changes with 

 fibrosis in workers handling nickel dust. Orsal nickel intake may 

 aggravate vesicular hand eczema. Prostheses or other surgical implants 

 make with nickel containing alloys have been reported to cause nickel 

 sensitization. Cancer rates have generally been close to normal in 

 stainless steel welding and nickel using industries, with the exception of 

 those involving exposure to chromium, particularly electroplating. 

 Nickel/cadmium battery workers exposed to high levels of both nickel and 

 cadmium may have resulted in a slightly increased risk of lung cancer. 

 Excesses of various cancers other than lung and nasal cancers such as 

 renal, gastric or prostatic have occasionally been reported in nickel 

 workers, but none have been found consistently. No increased cancer risk 

 has been demonstrated in workers exposed exclusively to metallic nickel. 

 The combined data on nickel alloy workers and gasseous diffusion workers, 

 all of whom were exposed to average concentrations of the order of 0.5 mg 

 nickel/cu m show no excess risk, though the total number of lung cancers 

 in these cohorts was to small to exclude a small increase in risk at this 

 level. [World Health Organization/International Programme on Chemical 

 Safety. Environmental Health Criteria 108 Nickel p.13 (1991)] **QC 

 REVIEWED** 

EVIDENCE FOR CARCINOGENICITY: 

 CLASSIFICATION: A; human carcinogen. BASIS FOR CLASSIFICATION: Human data 

 in which exposure to nickel refinery dust caused lung and nasal tumors in 

 sulfide nickel matte refinery workers in several epidemiologic studies in 

 different countries and on animal data in which carcinomas were produced 

 in rats by inhalation and injection. HUMAN CARCINOGENICITY DATA: 

 Sufficient. [U.S. Environmental Protection Agency's Integrated Risk 

 Information System (IRIS) on Nickel refinery dust (NO CAS RN) from the 

 National Library of Medicine's TOXNET System, March 1, 1995] **PEER 

 REVIEWED** 

 Evaluation: There is sufficient evidence in humans for the carcinogenicity 

 of nickel sulfate, and of the combinations of nickel sulfides and oxides 

 encountered in the nickel refining industry. There is inadequate evidence 

 in humans for the carcinogenicity of metallic nickel and nickel alloys. 

 There is sufficient evidence in experimental animals for the 

 carcinogenicity of metallic nickel, nickel monoxides, nickel hydroxides 

 and crystalline nickel sulfides. There is limited evidence in experimental 

 animals for the carcinogenicity of nickel alloys, nickelocene, nickel 

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 carbonyl, nickel salts, nickel arsenides, nickel antimonide, nickel 

 selenides and nickel telluride. There is inadequate evidence in 

 experimental animals for the carcinogenicity of nickel trioxide, amorphous 

 nickel sulfide and nickel titanate. The Working Group made the overall 

 evaluation on nickel compounds as a group on the basis of the combined 

 results of epidemiological studies, carcinogenicity studies in 

 experimental animals, and several types of other relevant data, supported 

 by the underlying concept that nickel compounds can generate nickel ions 

 at critical sites in their target cells. Overall evaluation: Nickel 

 compounds are carcinogenic to humans (Group 1). Metallic nickel is 

 possibly carcinogenic to humans (Group 2B). /Nickel compounds/ [IARC. 

 Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. 

 Geneva: World Health Organization, International Agency for Research on 

 Cancer, 1972-PRESENT. (Multivolume work)., p. V49 410 (1990)] **PEER 

 REVIEWED** 

 A5: Not suspected as a human carcinogen. [American Conference of 

 Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values 

 for Chemical Substances and Physical Agents and Biological Exposure 

 Indices. Cincinnati, OH, 2008, p. 43] **QC REVIEWED** 

 Metallic Nickel: is listed as reasonably anticipated to be a human 

 carcinogen. /Nickel Compounds and Metallic Nickel/ [DHHS/National 

 Toxicology Program; Eleventh Report on Carcinogens: Nickel Compounds and 

 Metallic Nickel (January 2005). Available from, as of July 31, 2009: 

 http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s118nick.pdf ] **QC 

 REVIEWED** 

HUMAN TOXICITY EXCERPTS: 

 NICKEL METAL IS WELL KNOWN CAUSE OF CONTACT DERMATITIS IN SENSITIZED 

 INDIVIDUALS. INSTANCES OF DERMATITIS IN REGION OF EYES HAS RESULTED FROM 

 CONTACT WITH NICKEL SPECTACLE FRAMES, BUT EYE ITSELF HAS NOT BEEN 

 INVOLVED. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: 

 Charles C. Thomas Publisher, 1986., p. 661] **PEER REVIEWED** 

 HISTOLOGICAL CHANGES IN NASAL MUCOSA OF NICKEL WORKERS WERE STUDIED. 

 [REITH A ET AL; ANN CLIN LAB SCI 8 (6): 503 (1978)] **PEER REVIEWED** 

 EPIDEMIOLOGICAL STUDIES CONCLUSIVELY DEMONSTRATE EXCESS RISK OF CANCER OF 

 NASAL CAVITY & LUNG IN WORKERS IN NICKEL REFINERIES. IT IS LIKELY THAT 

 NICKEL IN SOME FORM(S) IS CARCINOGENIC TO MAN. [IARC. Monographs on the 

 Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World 

 Health Organization, International Agency for Research on Cancer, 

 1972-PRESENT. (Multivolume work)., p. V11 104 (1976)] **PEER REVIEWED** 

 In nickel refinery workers, an excess risk of nasal and lung cancers has 

 been demonstrated. [USEPA; Ambient Water Quality Criteria Document: Nickel 

 p.C-105 (1980) EPA 400/5-80-060] **PEER REVIEWED** 

 Nickel, nickel subsulfide, and nickel oxide are generated in relatively 

 large particle sizes during the production & miniing of nickel & 

 are, thus, associated with damage to the nasal mucosa. [Doull, J., 

 C.D.Klassen, and M.D. Amdur (eds.). Casarett and Doull's Toxicology. 3rd 

 ed., New York: Macmillan Co., Inc., 1986., p. 352] **PEER REVIEWED** 

 /The investigators/ found no chromosomal aberrations after human 

 lymphocytes were treated in vitro with nickel oxide and nickel powder. No 

 doses or toxicity levels were given, and it is not clear whether the cells 

 had a significant exposure to these insol cmpd. [Friberg, L., Nordberg, 

 G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of 

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 Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 

 1986., p. V1 342] **PEER REVIEWED** 

 IN NICKEL PLATING INDUSTRY, EXPOSURE TO NICKEL CONTAINING VAPORS HAS BEEN 

 REPORTED TO BE ASSOC WITH ASTHMA. SYMPTOMS WERE ATTRIBUTED TO 

 HYPERSENSITIVITY TO NICKEL OF NON-OCCUPATIONAL ORIGIN. PNEUMOCONIOSIS HAS 

 BEEN REPORTED AMONG WORKERS EXPOSED TO NICKEL DUST ... EFFECTS ON NASAL 

 MEMBRANE WERE NOTED IN WORKERS EXPOSED TO NICKEL AEROSOLS IN AN 

 ELECTROLYSIS SHOP. /NICKEL VAPORS & DUST/ [Friberg, L., Nordberg, 

 G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of 

 Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 

 1986., p. V2 473] **PEER REVIEWED** 

 WORKERS EMPLOYED IN NICKEL PLATING HAVE DEVELOPED CONJUNCTIVITIS & 

 EPIPHORA WHEN VENTILATION WAS POOR. [Grant, W.M. Toxicology of the Eye. 

 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 661] 

 **PEER REVIEWED** 

 NICKEL AS INDUSTRIAL INHALANT WAS FIRST SUSPECTED AS CARCINOGEN IN BRONCHI 

 IN 1933, ESTABLISHED BOTH EPIDEMIOLOGICALLY & EXPERIMENTALLY; FIRST AS 

 CARCINOGEN IN NASAL CAVITY IN 1933, ESTABLISHED EPIDEMIOLOGICALLY BUT 

 NEGATIVE RESULTS EXPERIMENTALLY. /FROM TABLE/ [Searle, C. E. (ed.). 

 Chemical Carcinogens. ACS Monograph 173. Washington, DC: American Chemical 

 Society, 1976., p. 327] **PEER REVIEWED** 

 ... TOXIC AS DUST OR POWDER. [Sax, N.I. and R.J. Lewis, Sr. (eds.). 

 Hawley's Condensed Chemical Dictionary. 11th ed. New York: Van Nostrand 

 Reinhold Co., 1987., p. 818] **PEER REVIEWED** 

 The mortality of a cohort of 2689 nickel/chromium platers between 1946 and 

 1983 was investigated. All members of the study cohort had some /exposure 

 to chrome during their/ employment. Overall, /when/ compared with the 

 general population of England and Wales, statistically significant 

 differences relating to cancer were found for cancer of the stomach (E= 

 16.2, 0= 25), primary cancer of the liver (E= 0.8, 0= 4), cancer of the 

 nose and nasal cavities (E= 0.3, 0= 3), cancers of the lung and bronchus 

 (E= 48.1, 0= 72), and all cancers (E= 164.2, 0= 213). Exposure to nickel 

 was shown not to be an important confounding effect. [Sorahan T et al; Br 

 J Ind Med 44 (4): 250-8 (1987)] **PEER REVIEWED** 

 Nickel sensitivity was detected in 176 cases out of 2400 patients at eight 

 patch test clinics in five eastern European countries. Each clinic tested 

 300 consecutive patients. Of the positive responses obtained, 89.2 percent 

 occured in females; only 2.1 percent of tested men were nickel sensitive. 

 Nickel dermatitis appeared to be a disorder primarily of schoolgirls and 

 women younger than 25 yr. Exposure to nickel in 49 percent of the cases 

 was for 1 yr or less. Occupational contact was not significant in 75 

 percent of the cases. Jewelry was the cause in 31.8 percent of the 

 patients, wrist watches and their straps in 23.3 percent, and clothing 

 buckles in 6.3 percent. Buttons on jeans were also a common cause. 

 Occupational causes were cited in 44 cases, with the main source of 

 exposure being scissors, medical instruments, kitchen articles, and 

 plating solution. A secondary role was played by coins. Hands and wrists 

 were predominant sites for dermatitis. [Schubert H et al; Contact 

 Dermatitis 16 (3): 122-8 (1987)] **PEER REVIEWED** 

 Employees of the heat seal department at COSCO Inc (SIC-2519), Columbus, 

 Indiana, complained of eye, nose, and throat irritation plus skin rashes 

 and a burning sensation on the lips. Breathing zone monitoring of welders 

 indicated that one was exposed to excessive levels (37 micrograms/cu m) of 

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 airborne nickel. [Hartle RW, Albrect W; Govt Reports Announcements & 

 Index (GRA & I) 23 (1987)] **PEER REVIEWED** 

 Of 557 patients with occupational dermatoses seen at the Middle Road 

 Hospital, Singapore, 55.7% were irritant contact dermatitis, 38.6% were 

 allergic contact dermatitis, and 5.7% were non-contact dermatitis. More 

 than half of the patients were below 30 years old and most were from the 

 construction (29.5%), metal/engineering (20.6%), electrical/electronic 

 (16.4%), transport (5.5%), and food catering (3.8%) industries. Resins 

 including epoxy, acrylate and paratertiary butyl phenol resins and other 

 metals (nickel and cobalt) were occupational allergens. [Goh CL; Ann Acad 

 Med Singapore 16 (2): 303-5 (1987)] **PEER REVIEWED** 

 A worker who coated pipes with synthetic rubber showed no reaction to 

 rubber or rubber chemicals in patch tests, but showed strong positive 

 reactions to nickel and chromium. Investigation indicated that he worked 

 near 2 metal spraying areas where airborne nickel levels were 4 times 

 higher and chromium up to 18 times higher than the UK Health and Safety 

 Executive recommended maximum time weighted averages. [Handfield Jones S 

 et al; Contact Dermatitis 16 (1): 44 (1987)] **PEER REVIEWED** 

 A mortality study and an incidence study for laryngeal cancer, was 

 conducted on 361 men (minimum employment, one year) in the Italian soap 

 production industries. Employment in this industry includes some exposure 

 to sulfuric acid vapors and nickel dusts. Mortality from all causes was 

 lower than expected; lung cancer and laryngeal cancer deaths showed 

 nonsignificant increases. Five new laryngeal cancer cases were detected 

 during the study period. All the men with respiratory cancer had been 

 working for several years, and the latency time was greater than 10 years. 

 [Forastiere F et al; Scand J Work Environ Health 13 (3): 258-60 (1987)] 

 **PEER REVIEWED** 

 Occupational cancers of the respiratory tract were reviewed, and the 

 historical development of lung cancer as an occupational disease was 

 summarized. A variety of etiologic agents in occupational lung cancer were 

 discussed including arsenic, asbestos, beryllium, chloromethyl ethers, 

 chromium compounds, polycyclic aromatic hydrocarbons, mustard gas, nickel, 

 ionizing radiation, and a variety of suspected carcinogens including vinyl 

 chloride, fibrous mineral materials, chloroprene, and vegetable dusts. 

 [Frank AL et al; Occup Med: State of the Art Rev 2 (1): 71-83 (1987)] 

 **PEER REVIEWED** 

 The contributions of sulfur dioxide and arsenic to lung cancer were 

 assessed in copper smelter workers with regard to the confounding variable 

 of cigarette smoking. The study included a total of 6,078 white male 

 workers who worked for a least 3 years in a USA copper smelter between the 

 dates of January 1, 1946, and December 31, 1976. Worker exposure to 

 arsenic, sulfur dioxide (SO2), dust, nickel, lead, and cadmium was 

 categorized by job and year. The percentage of the cohort alive at the end 

 of the study period was 73.9, and the standard mortality ratios relative 

 to three reference populations were comparable. Standard mortality ratios 

 revealed a dose response relationship between arsenic, sulfur dioxide 

 exposure and development of lung cancer. A nested case control analysis 

 showed cigarette smoking and arsenic exposure, but not sulfur dioxide 

 exposure, to be significant factors in the etiology of lung cancer in 

 smelter employees. [Enterline PE et al; J Occup Med 29 (10): 831-8 (1987)] 

 **PEER REVIEWED** 

 Galvanizer's eczema, a skin condition encountered among 40 workers engaged 

 in the electric coating of metals with other metals, particularly nickel 

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 coating, is discussed. An ointment is described for the treatment of the 

 condition, although prevention is essential. In addition to some 

 protective cream, mandatory preventive measures should be imposed for all 

 galvanizing operations. The physician's role is briefly outlined. 

 [Blaschko A; Deutsche Medizinische Wochenschrift 15: 925-7 (1989)] **PEER 

 REVIEWED** 

 Nickel, nickel subsulfide, and nickel oxide are generated in relatively 

 large sizes during the production & mining of nickel & are, thus, 

 associated with damage to the nasal mucosa. [Doull, J., C.D.Klassen, and 

 M.D. Amdur (eds.). Casarett and Doull's Toxicology. 3rd ed., New York: 

 Macmillan Co., Inc., 1986., p. 352] **PEER REVIEWED** 

 Nasal mucosal biopsy specimens from five normal individuals and 15 cases 

 of pathological epithelia were obtained from nickel workers. The 

 immunohistochemical detection of keratins was carried out using monoclonal 

 antibodies AE1 and AE3. The antibody AE1 stained only the basal cells of 

 normal mucociliary epithelium. All layers of the surface epithelium of 

 regular metaplasias were stained with AE3. The dysplastic and neoplastic 

 lesions exhibited an extraordinary increase in the staining patterns with 

 AE3 and to a lesser extent with AE1. Involucrin, which was absent from the 

 normal pseudostratified epithelium, appeared in all metaplastic dysplastic 

 lesions and in keratinized areas of carcinomas. The combined detection of 

 keratins and involucrin proved useful in detecting the degree of maturity 

 and differentiation of preneoplastic and neoplastic lesions of the nasal 

 mucosa. [Klein Szanto AJ et al; Arch Pathol Lab Med 3 (2): 1057-61 (1987)] 

 **PEER REVIEWED** 

 Seventy three nickel sensitive patients were patch tested with tin plated 

 discs for 48 hr, to identify metal alloys which are safe with respect to 

 nickel allergy. Copper discs were produced and a coating of pure tin was 

 plated onto the discs. A six week corrosion test using synthetic sweat at 

 30 deg C was conducted; nickel release was measured after 1, 3, and 6 

 weeks by atomic absorption spectrometry. Six patients had a positive 

 allergic reaction; four had equivocal positive reactions, and 63 patients 

 were negative. All patients had at least two other positive tests at the 

 same time. Retesting, done on the upper arm of one positive patient after 

 three months, confirmed the earlier observation. [Menne T et al; Contact 

 Dermatitis 16 (1): 9-10 (1987)] **PEER REVIEWED** 

 Delayed type hypersensitivity to nickel is one of the most common 

 allergies. About 4.5% of the general population in Europe and 5.8% in the 

 United States are allergic to this metal. Patch test clinics throughout 

 the world have a high prevalence of nickel sensitivity, in the range of 

 10% with a significantly rising prevalence in some European countries 

 approaching 20% to 30%. This is undoubtedly related to ear piercing. 

 [Marks, J.G. Jr., DeLeo V.A., Contact and Occupational Dermatology. St. 

 Louis, MO: Mosby Year Book 1992., p. 83] **PEER REVIEWED** 

 A recent study by Fischer et al. in Sweden showed that all metal pins used 

 for ear piercing released nickel in varying amounts, thus allowing 

 exposure to the antigen. Not only are women and schoolgirls affected, but 

 also men, now that ear piercing has become fashionable among them. Among 

 schoolgirls with pierced ears, 13% were allergic to nickel. In contrast, 

 only 1% without pierced ears exhibited nickel sensitivity. There is 

 conflicting evidence as to how good a history is at predicting nickel 

 sensitivity. Some studies have found a high correlation between a positive 

 nickel patch test response and a history of jewelry sensitivity. In one 

 study, 10 of 12 subjects developed dermatitis on the ears either shortly 

 after ear piercing or after wearing low quality pierced earrings. [Marks, 

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 J.G. Jr., DeLeo V.A., Contact and Occupational Dermatology. St. Louis, MO: 

 Mosby Year Book 1992., p. 83] **PEER REVIEWED** 

 Nickel is the most frequent metal which induces allergic contact 

 sensitization and accounts for approximately 10% of all positive patch 

 tests in North America. [Zenz, C., O.B. Dickerson, E.P. Horvath. 

 Occupational Medicine. 3rd ed. St. Louis, MO., 1994, p. 106] **PEER 

 REVIEWED** 

 Nickel hypersensitivity dermatitis may be initiated by contact with nickel 

 on the skin. Disulfiram metabolizes to dithiocarbamate and is an effective 

 nickel chelator in patients with nickel hypersensitivity dermatitis. 

 Nickel dermatitis may develop at previously affected sites during 

 initiation of disulfiram therapy for alcohol use. [Ellenhorn, M.J., S. 

 Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: 

 Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: 

 Williams and Wilkins, 1997., p. 1358] **PEER REVIEWED** 

 Asthma, urticaria, erythema multiforme, contact dermatitis, and hand 

 eczema may follow use of objects made with nickel. [Ellenhorn, M.J., S. 

 Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: 

 Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: 

 Williams and Wilkins, 1997., p. 1604] **PEER REVIEWED** 

 Nickel poisoning was reported in a group of 23 dialyzed patients, when 

 leaching from a nickel-plated stainless steel water heater tank 

 contaminated the dialysate. Symptoms occurred during, and after, dialysis, 

 at plasma-nickel concentrations of approximately 3 mg/litre. Symptoms 

 included nausea (37 out of 37), vomiting (31 out of 37), weakness (29 out 

 of 37), headache (22 out of 37), and palpitation (2 out of 37). Recovery 

 occurred spontaneously, generally 3-13 hr after cessation of dialysis ... 

 . [WHO; Environ Health Criteria 108: Nickel p.??? (1991)] **PEER 

 REVIEWED** 

 EXPOSURE TO INDUSTRIAL NICKEL DUST CAUSES NICKEL DERMATITIS. SENSITIVITY 

 TO NICKEL MAY BE EXHIBITED FROM SKIN CONTACT ... DIVALENT NICKEL IONS CAN 

 PENETRATE SKIN AT SWEAT-DUCT & HAIR FOLLICLE OSTIA, & BIND WITH 

 KERATIN. CONTACT DERMATITIS THUS RESULTS FROM PERMEABILITY OF ... DERMIS 

 & EPIDERMIS TO NICKEL. /NICKEL DUST & SALTS/ [Venugopal, B. and 

 T.D. Luckey. Metal Toxicity in Mammals, 2. New York: Plenum Press, 1978., 

 p. 292] **PEER REVIEWED** 

 An incr incidence of lung and nasal cavity cancers has been noted among 

 workmen in nickel smelters and refineries. /Nickel dust and compounds/ 

 [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial 

 Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-145] 

 **PEER REVIEWED** 

MEDICAL SURVEILLANCE: 

 PRECAUTIONS FOR "CARCINOGENS": ... In relation specifically to cancer 

 hazards, there are at present no health monitoring methods that may ensure 

 the early detection of preneoplastic lesions or lesions which may preclude 

 them. Whenever medical surveillance is indicated, in particular when 

 exposure to a carcinogen has occurred, ad hoc decisions should be taken 

 concerning additional tests that might become useful or mandatory. 

 /Chemical Carcinogens/ [Montesano, R., H. Bartsch, E.Boyland, G. Della 

 Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis 

 (eds.). Handling Chemical Carcinogens in the Laboratory: Problems of 

 Safety. IARC Scientific Publications No. 33. Lyon, France: International 

 Agency for Research on Cancer, 1979., p. 23] **PEER REVIEWED** 

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PROBABLE ROUTES OF HUMAN EXPOSURE: 

 Occupational exposures to nickel and its cmpd occur in (1) mining and 

 comminution of nickel containing ores; (2) nickel refining and smelting; 

 (3) nickel electroplating; (4) producing and using nickel catalysts; (5) 

 fabricating parts and structures by welding, flame spraying, cutting, 

 grinding, and polishing of nickel containing alloys; (6) manufacturing 

 nickel cadmium batteries; (7) constructing nickel molds in glass bottle 

 factories; (8) spraying nickel containing paints (eg, yellow nickel 

 titanate pigment); and (9) recycling or disposal of nickel containing 

 products. /Nickel and nickel cmpd/ [Seiler, H.G., H. Sigel and A. Sigel 

 (eds.). Handbook on the Toxicity of Inorganic Compounds. New York, NY: 

 Marcel Dekker, Inc. 1988., p. 455] **PEER REVIEWED** 

 IN NICKEL PLATING INDUSTRY, EXPOSURE TO NICKEL CONTAINING VAPORS HAS BEEN 

 REPORTED TO BE ASSOC WITH ASTHMA. SYMPTOMS WERE ATTRIBUTED TO 

 HYPERSENSITIVITY TO NICKEL OF NON-OCCUPATIONAL ORIGIN. PNEUMOCONIOSIS HAS 

 BEEN REPORTED AMONG WORKERS EXPOSED TO NICKEL DUST ... EFFECTS ON NASAL 

 MEMBRANE WERE NOTED IN WORKERS EXPOSED TO NICKEL AEROSOLS IN AN 

 ELECTROLYSIS SHOP. /NICKEL VAPORS & DUST/ [Friberg, L., Nordberg, 

 G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of 

 Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 

 1986., p. V2 473] **PEER REVIEWED** 

TOXICITY SUMMARY: 

 Nickel is a ubiquitous trace metal and occurs in soil, water, air and the 

 biosphere. Nickel ore deposits are accumulations of nickel sulfide 

 minerals (mostly pentlandite) and laterites. Most nickel is used for 

 production of stainless steel and other nickel alloys with high corrosion 

 and temperature resistance. Nickel levels in terrestrial and aquatic 

 organisms can vary over several orders of magnitude. Dermal exposure in 

 the general environment is important for the induction and maintenance of 

 contact hypersensitivity caused by daily contact with nickel plated 

 objects or nickel containing alloys (e.g. jewellery, coins or clips). 

 Iatrogenic exposure to nickel results from implants and prostheses made 

 from nickel containing alloys, from iv or dialysis fluids and from 

 radiographic contrast media. In the working environment, airborne nickel 

 concentrations can vary from a few microgram/cu m to a few mg/cu m, 

 depending upon the process involved and the nickel content of the material 

 being handled. Workers are exposed to nickel containing dusts and fumes 

 during welding, plating, grinding, mining, nickel refining, and in steel 

 plants. Dermal exposure to nickel may occur in a wide range of jobs, 

 either by direct exposure, dissolved nickel in refining, electroplating 

 and electroforming industries or by handling nickel containing materials. 

 Nickel can be absorbed in human beings and animals via inhalation or 

 ingestion or percutaneously. Respiratory absorption with secondary 

 gastrointestinal absorption (insoluble and soluble) is a major route of 

 entry during occupational exposure. Percutaneous absorption is negligible, 

 quantatively, but is important in the pathogenesis of contact 

 hypersensitivity. Nickel is transported in the blood, principally bound to 

 albumin. Gastrointestinal absorption of nickel is variable and depends on 

 the composition of the diet. All body secretions are potential routes of 

 excretion including the urine, bile, sweat, tears, milk and mucociliary 

 fluid. Non-absorbed nicke is eliminated in the feces. Data on nickel 

 excretion suggest a two compartment model. Nickel concentration in the 

 serum and urine of healthy non-occupationally exposed adults are 0.2 ug/l 

 (range: 0.05-1.1 ug/l) and 1.5 ug creatinine (range: 0.5-4.0 mg/g 

 creatinine, respectively. The body burden of nickel in non-exposed 70 kg 

 adult is 0.5 ug. Nickel is essential for the catalytic activity of some 

 plant and bacterial enzymes. Slow weight gain, anemia and decreased 

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 viability has been described in some animal species after dietary 

 deprivation of nickel. Contact allergy to nickel is very common in human 

 beings; experimental sensitization in animals is only successful under 

 special conditions. Longterm inhalation exposure to metallic nickel caused 

 mucosal damage and inflammatory reaction, sometimes accompanied by slight 

 fibrosis, was observed in rabbits after high level exposure to nickel 

 graphite dust. Metallic nickel induced local mesenchymal tumors in a 

 variety of experimental animals after im, sc, intraosseous, intrarenal, 

 intra-articular, pleural, intraocular, intratesticular or intra-adipose 

 administrtation. Metallic nickel has been tested for carcinogenicity by 

 parenteral routes of administration, local tumors were noted. In studies 

 using repeated intratracheal instillation, nickel powder caused 

 respiratory tumors. Chronic effects such as rhinitis, sinusitis, nasal 

 septal perforations and asthma have been reported in nickel refinery and 

 nickel plating workers. Some researchers reported pulmonary changes with 

 fibrosis in workers handling nickel dust. Orsal nickel intake may 

 aggravate vesicular hand eczema. Prostheses or other surgical implants 

 make with nickel containing alloys have been reported to cause nickel 

 sensitization. Cancer rates have generally been close to normal in 

 stainless steel welding and nickel using industries, with the exception of 

 those involving exposure to chromium, particularly electroplating. 

 Nickel/cadmium battery workers exposed to high levels of both nickel and 

 cadmium may have resulted in a slightly increased risk of lung cancer. 

 Excesses of various cancers other than lung and nasal cancers such as 

 renal, gastric or prostatic have occasionally been reported in nickel 

 workers, but none have been found consistently. No increased cancer risk 

 has been demonstrated in workers exposed exclusively to metallic nickel. 

 The combined data on nickel alloy workers and gasseous diffusion workers, 

 all of whom were exposed to average concentrations of the order of 0.5 mg 

 nickel/cu m show no excess risk, though the total number of lung cancers 

 in these cohorts was to small to exclude a small increase in risk at this 

 level. [World Health Organization/International Programme on Chemical 

 Safety. Environmental Health Criteria 108 Nickel p.13 (1991)] **QC 

 REVIEWED** 

EVIDENCE FOR CARCINOGENICITY: 

 CLASSIFICATION: A; human carcinogen. BASIS FOR CLASSIFICATION: Human data 

 in which exposure to nickel refinery dust caused lung and nasal tumors in 

 sulfide nickel matte refinery workers in several epidemiologic studies in 

 different countries and on animal data in which carcinomas were produced 

 in rats by inhalation and injection. HUMAN CARCINOGENICITY DATA: 

 Sufficient. [U.S. Environmental Protection Agency's Integrated Risk 

 Information System (IRIS) on Nickel refinery dust (NO CAS RN) from the 

 National Library of Medicine's TOXNET System, March 1, 1995] **PEER 

 REVIEWED** 

 Evaluation: There is sufficient evidence in humans for the carcinogenicity 

 of nickel sulfate, and of the combinations of nickel sulfides and oxides 

 encountered in the nickel refining industry. There is inadequate evidence 

 in humans for the carcinogenicity of metallic nickel and nickel alloys. 

 There is sufficient evidence in experimental animals for the 

 carcinogenicity of metallic nickel, nickel monoxides, nickel hydroxides 

 and crystalline nickel sulfides. There is limited evidence in experimental 

 animals for the carcinogenicity of nickel alloys, nickelocene, nickel 

 carbonyl, nickel salts, nickel arsenides, nickel antimonide, nickel 

 selenides and nickel telluride. There is inadequate evidence in 

 experimental animals for the carcinogenicity of nickel trioxide, amorphous 

 nickel sulfide and nickel titanate. The Working Group made the overall 

 evaluation on nickel compounds as a group on the basis of the combined 

 results of epidemiological studies, carcinogenicity studies in 

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 experimental animals, and several types of other relevant data, supported 

 by the underlying concept that nickel compounds can generate nickel ions 

 at critical sites in their target cells. Overall evaluation: Nickel 

 compounds are carcinogenic to humans (Group 1). Metallic nickel is 

 possibly carcinogenic to humans (Group 2B). /Nickel compounds/ [IARC. 

 Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. 

 Geneva: World Health Organization, International Agency for Research on 

 Cancer, 1972-PRESENT. (Multivolume work)., p. V49 410 (1990)] **PEER 

 REVIEWED** 

 A5: Not suspected as a human carcinogen. [American Conference of 

 Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values 

 for Chemical Substances and Physical Agents and Biological Exposure 

 Indices. Cincinnati, OH, 2008, p. 43] **QC REVIEWED** 

 Metallic Nickel: is listed as reasonably anticipated to be a human 

 carcinogen. /Nickel Compounds and Metallic Nickel/ [DHHS/National 

 Toxicology Program; Eleventh Report on Carcinogens: Nickel Compounds and 

 Metallic Nickel (January 2005). Available from, as of July 31, 2009: 

 http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s118nick.pdf ] **QC 

 REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 Occupational exposures to nickel and its cmpd occur in (1) mining and 

 comminution of nickel containing ores; (2) nickel refining and smelting; 

 (3) nickel electroplating; (4) producing and using nickel catalysts; (5) 

 fabricating parts and structures by welding, flame spraying, cutting, 

 grinding, and polishing of nickel containing alloys; (6) manufacturing 

 nickel cadmium batteries; (7) constructing nickel molds in glass bottle 

 factories; (8) spraying nickel containing paints (eg, yellow nickel 

 titanate pigment); and (9) recycling or disposal of nickel containing 

 products. /Nickel and nickel cmpd/ [Seiler, H.G., H. Sigel and A. Sigel 

 (eds.). Handbook on the Toxicity of Inorganic Compounds. New York, NY: 

 Marcel Dekker, Inc. 1988., p. 455] **PEER REVIEWED** 

 IN NICKEL PLATING INDUSTRY, EXPOSURE TO NICKEL CONTAINING VAPORS HAS BEEN 

 REPORTED TO BE ASSOC WITH ASTHMA. SYMPTOMS WERE ATTRIBUTED TO 

 HYPERSENSITIVITY TO NICKEL OF NON-OCCUPATIONAL ORIGIN. PNEUMOCONIOSIS HAS 

 BEEN REPORTED AMONG WORKERS EXPOSED TO NICKEL DUST ... EFFECTS ON NASAL 

 MEMBRANE WERE NOTED IN WORKERS EXPOSED TO NICKEL AEROSOLS IN AN 

 ELECTROLYSIS SHOP. /NICKEL VAPORS & DUST/ [Friberg, L., Nordberg, 

 G.F., Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of 

 Metals. 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 

 1986., p. V2 473] **PEER REVIEWED** 

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The following information was generated from the 

Hazardous Substances Data Bank (HSDB), 

a database of the National Library of Medicine's TOXNET system 

(http://toxnet.nlm.nih.gov) on October 27, 2009. 

Query: The chemical name selenium was identified. 

The following terms were added from ChemIDplus: 

selenium homopolymer 

selenium elemental 

selenium dust 

selenium base 

selenium alloy 

selen 

elemental selenium 

CAS Registry Number: 7782-49-2 

1 

NAME: SELENIUM, ELEMENTAL 

RN: 7782-49-2 

NOTE: 

 This record contains information for selenium in its zero valence state 

 only. For general toxicology and environmental fate of selenium ions and 

 selenium compounds, refer to the SELENIUM COMPOUNDS record; for 

 compound-specific information, refer to the appropriate individual 

 records, e.g., hydrogen selenide, selenium hexafluoride, etc. 

HUMAN HEALTH EFFECTS: 

TOXICITY SUMMARY: 

 Selenium is an essential trace element and has been shown to be a natural 

 component in the enzyme glutathione peroxidase and other proteins. Most 

 selenium compounds are water-soluble and can efficiently be taken up in 

 the intestine. Soluble as well as non-soluble compounds can be taken up by 

 the lungs. When given in excess, selenium compounds are rapidly 

 distributed to major organs of the body. ... Identified metabolites are 

 trimethylselenide in urine and dimethylselenide in breath. ... in man ... 

 toxic effects have been reported at 1 mg/dl. ... Toxic effects have been 

 seen at blood levels ranging from 0.179 ug/ml-7.5 ug/ml. In most parts of 

 the world normal urine levels do not exceed 0.03 ug/ml. Occupationally 

 exposed workers usually excrete less than 0.1 ug/ml. The LD50 ranges 

 between 1.5 and 6 mg/kg for many selenium compounds and animal species. 

 The CNS seems to be the target organ ... but the liver, heart, and lungs 

 may also be affected. A few cases of selenium poisoning in humans have 

 been described ... either after consumption of selenium or after exposure 

 via inhalation. Gastrointestinal and neurological symptoms predominated. 

 Chronic poisoning due to long term exposure has been reported in livestock 

 and humans from geographical areas where soil contains high levels of 

 selenium. In rodent liver cirrhosis is a common effect while typical 

 effects in domestic animals are: emaciation, deformation of hooves, loss 

 of hair, and joint erosions. In humans consuming 5 mg selenium per day, 

 hair and nail problems are very common. Skin lesions and depigmentation 

 are also common signs of intoxication. In more severe cases neurological 

 and gastrointestinal symptoms predominate. ... Several selenium compounds 

 have been tested for possible carcinogenic potential. Selenium sulfide has 

 been shown to induce liver cancer in two species while no convincing 

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 evidence of carcinogenicity has been presented for other selenium 

 compounds. ... Some selenium compounds may induce DNA damage and some 

 previous reports indicate a teratogenic potential ... . Selenium may 

 prevent or alleviate toxic effects of arsenic, cadmium, mercury, platinum, 

 and silver. Conversely, some of these metals protect against selenium 

 toxicity. [J. Hogberg and J. Alexander. "Selenium" p 482 in Handbook on 

 the Toxicology of Metals, 2nd edition, ed by L. Friberg et al. Elsevier 

 Science Publishers (1986)] **PEER REVIEWED** 

EVIDENCE FOR CARCINOGENICITY: 

 CLASSIFICATION: D; not classifiable as to human carcinogenicity. BASIS FOR 

 CLASSIFICATION: Based on inadequate human data and inadequate evidence of 

 carcinogenicity in animals. The evidence for various selenium compounds in 

 animal and mutagenicity studies is conflicting and difficult to interpret; 

 however, evidence for selenium sulfide is sufficient for a B2 (probable 

 human carcinogen) classification. HUMAN CARCINOGENICITY DATA: Inadequate. 

 ANIMAL CARCINOGENICITY DATA: Inadequate. [U.S. Environmental Protection 

 Agency's Integrated Risk Information System (IRIS) on Selenium and 

 compounds (7782-49-2) Available from: http://www.epa.gov/ngispgm3/iris on 

 the Substance File List as of March 15, 2000] **PEER REVIEWED** 

 Classification of carcinogenicity: 1) evidence in humans: inadequate; 2) 

 evidence in animals: inadequate. Summary evaluation of carcinogenic risk 

 to humans 3: The agent is not classifiable as to its carcinogenicity to 

 humans. /From table, Selenium and selenium compounds/ [IARC. Monographs on 

 the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World 

 Health Organization, International Agency for Research on Cancer, 

 1972-PRESENT. (Multivolume work)., p. S7 71 (1987)] **PEER REVIEWED** 

HUMAN TOXICITY EXCERPTS: 

 ACUTE INDUSTRIAL EXPOSURE TO ELEMENTAL SELENIUM PRODUCED MUCOUS MEMBRANE 

 IRRITATION, SNEEZING, COUGHING, REDNESS OF EYE, & IN HEAVILY EXPOSED 

 WORKERS, DIFFICULTY IN BREATHING, FRONTAL HEADACHES, & DYSPNEA. ... 

 POSSIBLE THAT SOME SELENIUM DIOXIDE WAS FORMED IN MFR PROCESS INVOLVED. IN 

 SOME INSTANCES WORKERS HAVE REPORTED DERMATITIS ON THE BACKS OF THEIR 

 HANDS. [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial 

 Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: 

 John Wiley Sons, 1981-1982., p. 2131] **PEER REVIEWED** 

 ... SIGNS OF OCCUPATIONAL DISEASE RESULTING FROM LONG TERM INDUSTRIAL 

 EXPOSURE TO SELENIUM /INCLUDE/ BRONCHIAL IRRITATION, GI DISTRESS, 

 NASOPHARYNGEAL IRRITATION, & PERSISTENT GARLIC ODOR ON BREATH. THIS 

 ODOR, HOWEVER, IS NOT RELIABLE AND MAY BE PRESENT WHEN URINARY EXCRETION 

 IS AS HIGH AS 0.1 MG/L. ... METALLIC TASTE ALSO REPORTED ... IN CHRONIC 

 INDUSTRIAL EXPOSURE. OTHER SIGNS INCLUDE PALLOR, IRRITABILITY, AND 

 EXCESSIVE FATIGUE. [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial 

 Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th 

 ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 797] **PEER 

 REVIEWED** 

 Long-term Exposure: Prolonged exposure to selenium, sodium selenite, 

 sodium selenate, or selenium dioxide may cause paleness, coated tongue, 

 stomach disorders, nervousness, metallic taste and a garlic odor of the 

 breath. [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). 

 NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. 

 DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. 

 Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED** 

 /Elemental selenium/ is nontoxic in therapeutic doses (50-200 ug/day), 

 with a normal daily intake in one study of 81 ug. The estimated ingested 

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 dose of superpotent /elemental/ selenium in a series of toxic cases ranged 

 from 27 to 2,310 mg, with nausea, vomiting, nail changes, fatigue, and 

 irritability as the most common manifestations. /Elemental/ selenium dusts 

 produce respiratory tract irritation manifested by nasal discharge, loss 

 of smell, epistaxis, and cough. [Ellenhorn, M.J., S. Schonwald, G. Ordog, 

 J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment 

 of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 

 1607] **PEER REVIEWED** 

 Human whole blood cultures were exposed to selenium dioxide and selenium 

 in other valence states. The ability of the Se cmpd to induce sister 

 chromatid exchanges in decreasing order of their effectiveness were: Se, 

 selenium dioxide, sodium selenide, sodium selenite, and sodium selenate. 

 [Ray JH, Altenburg LC; Mutat Res 78 (3): 261-6 (1980)] **PEER REVIEWED** 

 ... A 35 year old woman who ate approximately 10 g of a breakfast cereal 

 to which selenium (35 mg/g) in some unknown form had been added. One year 

 later when the analysis was carried out, 12 mg/g was in the form of 

 selenite and the rest probably in the form of elemental selenium. She 

 vomited, had diarrhea, cramps, and felt numbness in her arms 30 min after 

 intake. She recovered within days, but later experienced irregular 

 menstrual bleedings and a marked hair loss. Hair analysis (neutron 

 activation) was performed 13 months later. [Friberg, L., Nordberg, G.F., 

 Kessler, E. and Vouk, V.B. (eds). Handbook of the Toxicology of Metals. 

 2nd ed. Vols I, II.: Amsterdam: Elsevier Science Publishers B.V., 1986., 

 p. 499] **PEER REVIEWED** 

 Routes of entry: Inhalation of dust or vapor, percutaneous absorption of 

 liquid, ingestion, eye and skin contact. /Selenium and cmpds/ [Sittig, M. 

 Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. 

 Park Ridge, NJ: Noyes Data Corporation, 1985., p. 778] **PEER REVIEWED** 

 

 Symptoms demonstrated by humans suffering from chronic selenium 

 intoxication include depression, languor, nervousness, dermatitis, 

 gastrointestinal disturbances, giddiness, garlic odor of the breath and 

 sweat, moderate emotional instability, excess dental caries, and in 

 extreme cases, loss of fingernails and partial alopecia. /Selenium and 

 cmpd/ [American Conference of Governmental Industrial Hygienists, Inc. 

 Documentation of the Threshold Limit Values and Biological Exposure 

 Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 

 1354] **PEER REVIEWED** 

 The elemental forms of selenium are probably completely harmless to man; 

 its compounds, however, are dangerous and their action resembles that of 

 sulfur compounds. /Selenium compounds/ [International Labour Office. 

 Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, 

 Switzerland: International Labour Office, 1983., p. 2018] **PEER 

 REVIEWED** 

 ACUTE POISONING THROUGH INHALATION MAY OCCUR IN INDUSTRY (SELENIUM DUST 

 & FUMES, SELENIUM DIOXIDE & HYDROGEN SELENIDE). ... GARLICKY 

 BREATH ODOR... IRRITATION OF MUCOUS MEMBRANES OF EYES, THROAT & LUNGS, 

 & SKIN DAMAGE...FROM DIRECT CONTACT (BURNS, DERMATITIS). NO INCR OR 

 DECR IN INCIDENCE OF CANCER... /SELENIUM COMPOUNDS/ [Friberg, L., G.R. 

 Nordberg, and V.B. Vouk. Handbook on the Toxicology of Metals. New York: 

 Elsevier North Holland, 1979., p. 556] **PEER REVIEWED** 

 ...SELENIUM POISONING /SYMPTOMS/ DUE TO INHALATION OF SELENIUM FUMES OR... 

 DUST...INCL...NAUSEA & VOMITING, INDIGESTION & OTHER INTERNAL 

 DISTURBANCES; INCR BODY TEMP, HEADACHE, LASSITUDE & ILL-DEFINED 

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 PSYCHONEUROTIC SYMPTOMS, SUCH AS IRRITABILITY. UNSTABLE BLOOD 

 PRESSURE...LYMPHOCYTOSIS...YELLOWISH SKIN... /SELENIUM COMPD/ [Friberg, 

 L., G.R. Nordberg, and V.B. Vouk. Handbook on the Toxicology of Metals. 

 New York: Elsevier North Holland, 1979., p. 568] **PEER REVIEWED** 

 ... PORPHYRINURIA ACCOMPANYING SEVERE SKIN LESIONS IN A GLASS WORKER, WHO 

 HAD INHALED DUST OF SELENIUM & SODIUM SELENITE, WAS /ASSUMED/ 

 ASSOCIATED WITH A LATENT DISPOSITION ACTIVATED BY ACTION OF SELENIUM. 

 [Browning, E. Toxicity of Industrial Metals. 2nd ed. New York: 

 Appleton-Century-Crofts, 1969., p. 293] **PEER REVIEWED** 

SKIN, EYE AND RESPIRATORY IRRITATIONS: 

 ... /Elemental/ selenium dusts produce respiratory tract irritation 

 manifested by nasal discharge, loss of smell, epistaxis, and cough. 

 [Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's 

 Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. 

 Baltimore, MD: Williams and Wilkins, 1997., p. 1607] **PEER REVIEWED** 

MEDICAL SURVEILLANCE: 

 The following medical procedures should be made available to each employee 

 who is exposed to selenium and its inorganic compounds at potentially 

 hazardous levels: 1. Initial Medical Examination: A complete history and 

 physical examination: The purpose is to detect existing conditions that 

 might place the exposed employee at increased risk, and to establish a 

 baseline for future health monitoring. Persons with a history of asthma, 

 allergies, or known sensitization to selenium, or with a history of other 

 chronic respiratory disease, gastrointestinal disturbances, disorders of 

 liver or kidneys or recurrent dermatitis would be expected to be at 

 increased risk from exposure. Examination of the eyes, respiratory system, 

 liver, kidneys, and blood should be stressed. The skin should be examined 

 for evidence of chronic disorders. Special consideration should be given 

 to women of childbearing age since the possibility that selenium may be 

 teratogenic might place these women in a high risk group. Urinalysis: 

 Proper function of the kidneys is necessary to validate levels of selenium 

 in the urine. A urinalysis should be obtained to include at a minimum 

 specific gravity, albumin, glucose, and a microscopic /examination of/ 

 centrifuged sediment. Liver function tests: Selenium causes liver damage 

 and tumors in animals. A profile of liver function should be obtained by 

 using a medically acceptable array of biochemical tests. The 

 aforementioned medical examinations should be repeated on an annual basis. 

 /Selenium and its inorganic compounds/ [Mackison, F. W., R. S. Stricoff, 

 and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health 

 Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 

 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 1] 

 **PEER REVIEWED** 

TOXICITY SUMMARY: 

 Selenium is an essential trace element and has been shown to be a natural 

 component in the enzyme glutathione peroxidase and other proteins. Most 

 selenium compounds are water-soluble and can efficiently be taken up in 

 the intestine. Soluble as well as non-soluble compounds can be taken up by 

 the lungs. When given in excess, selenium compounds are rapidly 

 distributed to major organs of the body. ... Identified metabolites are 

 trimethylselenide in urine and dimethylselenide in breath. ... in man ... 

 toxic effects have been reported at 1 mg/dl. ... Toxic effects have been 

 seen at blood levels ranging from 0.179 ug/ml-7.5 ug/ml. In most parts of 

 the world normal urine levels do not exceed 0.03 ug/ml. Occupationally 

 exposed workers usually excrete less than 0.1 ug/ml. The LD50 ranges 

 between 1.5 and 6 mg/kg for many selenium compounds and animal species. 

 The CNS seems to be the target organ ... but the liver, heart, and lungs 

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 may also be affected. A few cases of selenium poisoning in humans have 

 been described ... either after consumption of selenium or after exposure 

 via inhalation. Gastrointestinal and neurological symptoms predominated. 

 Chronic poisoning due to long term exposure has been reported in livestock 

 and humans from geographical areas where soil contains high levels of 

 selenium. In rodent liver cirrhosis is a common effect while typical 

 effects in domestic animals are: emaciation, deformation of hooves, loss 

 of hair, and joint erosions. In humans consuming 5 mg selenium per day, 

 hair and nail problems are very common. Skin lesions and depigmentation 

 are also common signs of intoxication. In more severe cases neurological 

 and gastrointestinal symptoms predominate. ... Several selenium compounds 

 have been tested for possible carcinogenic potential. Selenium sulfide has 

 been shown to induce liver cancer in two species while no convincing 

 evidence of carcinogenicity has been presented for other selenium 

 compounds. ... Some selenium compounds may induce DNA damage and some 

 previous reports indicate a teratogenic potential ... . Selenium may 

 prevent or alleviate toxic effects of arsenic, cadmium, mercury, platinum, 

 and silver. Conversely, some of these metals protect against selenium 

 toxicity. [J. Hogberg and J. Alexander. "Selenium" p 482 in Handbook on 

 the Toxicology of Metals, 2nd edition, ed by L. Friberg et al. Elsevier 

 Science Publishers (1986)] **PEER REVIEWED** 

EVIDENCE FOR CARCINOGENICITY: 

 CLASSIFICATION: D; not classifiable as to human carcinogenicity. BASIS FOR 

 CLASSIFICATION: Based on inadequate human data and inadequate evidence of 

 carcinogenicity in animals. The evidence for various selenium compounds in 

 animal and mutagenicity studies is conflicting and difficult to interpret; 

 however, evidence for selenium sulfide is sufficient for a B2 (probable 

 human carcinogen) classification. HUMAN CARCINOGENICITY DATA: Inadequate. 

 ANIMAL CARCINOGENICITY DATA: Inadequate. [U.S. Environmental Protection 

 Agency's Integrated Risk Information System (IRIS) on Selenium and 

 compounds (7782-49-2) Available from: http://www.epa.gov/ngispgm3/iris on 

 the Substance File List as of March 15, 2000] **PEER REVIEWED** 

 Classification of carcinogenicity: 1) evidence in humans: inadequate; 2) 

 evidence in animals: inadequate. Summary evaluation of carcinogenic risk 

 to humans 3: The agent is not classifiable as to its carcinogenicity to 

 humans. /From table, Selenium and selenium compounds/ [IARC. Monographs on 

 the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World 

 Health Organization, International Agency for Research on Cancer, 

 1972-PRESENT. (Multivolume work)., p. S7 71 (1987)] **PEER REVIEWED** 

SKIN, EYE AND RESPIRATORY IRRITATIONS: 

 ... /Elemental/ selenium dusts produce respiratory tract irritation 

 manifested by nasal discharge, loss of smell, epistaxis, and cough. 

 [Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's 

 Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. 

 Baltimore, MD: Williams and Wilkins, 1997., p. 1607] **PEER REVIEWED** 

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The following information was generated from the 

Hazardous Substances Data Bank (HSDB), 

a database of the National Library of Medicine's TOXNET system 

(http://toxnet.nlm.nih.gov) on October 27, 2009. 

Query: Records containing the word silver 

Singular and plural forms were searched. 

3 

NAME: SILVER, ELEMENTAL 

RN: 7440-22-4 

NOTE: 

 This record contains information for silver in its zero valence state 

 only. For general toxicity and environmental fate of silver ions and 

 silver compounds, refer to the SILVER COMPOUNDS record; for compound 

 specific information, refer to the appropriate individual records, e.g., 

 silver nitrate, silver iodide, etc. 

HUMAN HEALTH EFFECTS: 

EVIDENCE FOR CARCINOGENICITY: 

 CLASSIFICATION: D; not classifiable as to human carcinogenicity. BASIS FOR 

 CLASSIFICATION: In animals local sarcomas have been induced after 

 implantation of foils and disks of silver. However, the interpretation of 

 these findings has been questioned due to the phenomenon of solid-state 

 carcinogenesis in which even insoluble solids such as plastic have been 

 shown to result in local fibrosarcomas. ANIMAL CARCINOGENICITY DATA: 

 Inadequate . [U.S. Environmental Protection Agency's Integrated Risk 

 Information System (IRIS) on Silver (7440-22-4) Available from: 

 http://www.epa.gov/ngispgm3/iris on the Substance File List as of March 

 15, 2000] **PEER REVIEWED** 

HUMAN TOXICITY EXCERPTS: 

 IN INDUSTRY ARGYRIA FOLLOWING EXPOSURE TO SILVER MAY BE LOCALIZED OR 

 GENERALIZED. LOCALIZED FORM OCCURS CHIEFLY DURING HANDLING OF METALLIC 

 SILVER, WHEN PARTICLES BECOME IMBEDDED IN SKIN & SC TISSUES, EYE 

 LESIONS MAY ALSO BE MANIFESTATION. ... [Browning, E. Toxicity of 

 Industrial Metals. 2nd ed. New York: Appleton-Century-Crofts, 1969., p. 

 298] **PEER REVIEWED** 

 A LOCALIZED BLACKISH DISCOLORATION & /TISSUE MASS/ OF CONJUNCTIVA 

 DEVELOPED IN PATIENT'S EYE MANY YEARS AFTER SMALL SILVER INSTRUMENT HAD 

 BEEN ACCIDENTALLY LEFT IN TISSUES AT SITE OF OPERATION FOR STRABISMUS. 

 [Grant, W. M. Toxicology of the Eye. 2nd ed. Springfield, Illinois: 

 Charles C. Thomas, 1974., p. 910] **PEER REVIEWED** 

 ... Formation of a meningioma was found surrounding a silver clip left 

 from an operation two years before to remove an ependymoma in the brain of 

 an eleven year old girl. [USEPA; Ambient Water Quality Criteria Doc: 

 Silver p.C-114 (1980) EPA 440/5-80-071] **PEER REVIEWED** 

 Silver concentrations in human tissues apparently increase with age. It 

 has been detected in fetal livers and placentae. [Robkin MA et al; Trans 

 Am Nucl Soc 17: 97 (1973) as cited in USEPA; Ambient Water Quality 

 Criteria Doc: Silver p.C-1 (1980) EPA 440/5-80-071] **PEER REVIEWED** 

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 A striking feature of argyria is the regular deposition of silver in blood 

 vessels and connective tissue, especially around the face, conjunctiva, 

 hands, and fingernails. [Hill WR Pillsbury DM; Argyia, the Pharmacology of 

 Silver (1939) as cited in USEPA; Ambient Water Quality Criteria Doc: 

 Silver p.C-42 (1980) EPA 440/5-80-071] **PEER REVIEWED** 

 A nephrotic syndrome in an obese, argyric 73 yr old man was attributed to 

 silver deposits in the kidney. The man had used a silver containing 

 mouthwash or gargle for 10 years (1955-1965), presumably corresponding to 

 the absorption of a total amount of 88 g of silver. The patient showed 

 respiratory insufficiency and a nephrotic syndrome with proteinuria, 

 elevated alpha-2 macroglobulins, and glomerular (but not tubular) 

 involvement. Silver deposits were found in the glomerular basement 

 membrane. [Zech P et al; Nouv Presse Med 2: 161 (1973) as cited in USEPA; 

 Ambient Water Quality Criteria Doc: Silver p.C-79 (1980) EPA 440/5-80-071] 

 **PEER REVIEWED** 

 Collargol was used /iv/ to fill the renal pelvis for X-ray study and 

 resulted in severe hemorrhagic diathesis with parenchymatous hemorrhages 

 in the stomach, intestines, and body cavities ending in death. /Argyrol/ 

 [Hill WR, Pillsbury DM; Argyria, the Pharmacology of Silver (1939) as 

 cited in USEPA; Ambient Water Quality Criteria Doc: Silver p.C-69 (1980) 

 EPA 440/5-80-071] **PEER REVIEWED** 

 METALLIC SILVER MAY BE INHALED BY SILVER FINISHERS LEADING TO ABNORMAL 

 CHEST X-RAY FINDINGS. ... ITS IMPORTANCE LIES IN FAILURE TO RECOGNIZE 

 CAUSE OF SUCH X-RAY CHANGES RESULTING IN UNNECESSARY DIAGNOSTIC STUDIES OR 

 EXCLUSION FROM EMPLOYMENT. [Hamilton, A., and H. L. Hardy. Industrial 

 Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974., 

 p. 171] **PEER REVIEWED** 

 ... DEVELOPMENT /OF ARGYRIA (POISONING BY SILVER OR A SILVER SALT WHICH 

 LEADS TO A PERMANENT ASHEN-GRAY DISCOLORATION OF THE SKIN, CONJUNCTIVA, 

 AND INTERNAL ORGANS)/ FROM INHALATION THROUGH OCCUPATIONAL EXPOSURE 

 APPEARS TO BE VERY SLOW & MAY REQUIRE YEARS. [American Conference of 

 Governmental Industrial Hygienists, Inc. Documentation of the Threshold 

 Limit Values, 4th ed., 1980. Cincinnati, Ohio: American Conference of 

 Governmmental Industrial Hygienists, Inc., 1980., p. 367] **PEER 

 REVIEWED** 

 There is no evidence that silver or its compounds are carcinogenic to man. 

 [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and 

 Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley 

 Sons, 1981-1982., p. 1888] **PEER REVIEWED** 

 Silver in metallic form is harmless with the possible exception of 

 colloidal silver preparations. [Seiler, H.G., H. Sigel and A. Sigel 

 (eds.). Handbook on the Toxicity of Inorganic Compounds. New York, NY: 

 Marcel Dekker, Inc. 1988., p. 922] **PEER REVIEWED** 

 Silver may be a cause of metal fume fever. [Haddad, L.M. and Winchester, 

 J.F. Clinical Management of Poisoning and Drug Overdosage. Philadelphia, 

 PA: W.B. Saunders Co., 1983., p. 662] **PEER REVIEWED** 

 High local concn of silver from a prosthetic cement were associated with a 

 slowly resolving focal neuropathy. [Ellenhorn, M.J. and D.G. Barceloux. 

 Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, 

 NY: Elsevier Science Publishing Co., Inc. 1988., p. 1060] **PEER 

 REVIEWED** 

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 10 cc of a 2% solution were administered intravenously (Collargol). 

 Survival time was five minutes resulting in cyanosis, coma; death due to 

 pulmonary edema. There was no silver found in the lung. [Hill WR, 

 Pillsbury DM; Argyria, the Pharmacology of Silver (1939) as cited in 

 USEPA; Ambient Water Quality Criteria Doc: Silver p.C-69 (1980) EPA 

 440/5-80-071] **PEER REVIEWED** 

 Case reports were cited for four radiographers who were placed in danger 

 due to the x-ray processing chemical fumes present in their workspace. 

 These four cases encompass nearly all the 19 symptoms which have been 

 associated with reactions to chemical fumes: severe headaches, sore 

 throat/hoarseness, nasal discharge, sore eyes, unexpected fatigue, sinus 

 problems, nausea, painful joints, bad taste in mouth, mouth ulcers, 

 catarrh, tinnitus, tight chest, skin rash, lip sores, shortness of breath, 

 unusual heart rhythms, chest pains, and numb extremities. Three of the 

 four workers eventually had to give up work in radiography, and continued 

 to experience sensitivity to radiographic chemicals and other substances 

 such as automotive exhausts, cigarette smoke, paint fumes and red wine. 

 The fourth radiographer was engaged in silver recovery starting in 1958; 

 he suffered upper respiratory symptoms and recurring bouts of unexplained 

 pneumonia starting in 1970 until 1983 when he started to use a full face 

 mask and canister during silver recovery. [Gordon M; Radiography 53 (608): 

 85-9 (1987)] **PEER REVIEWED** 

 A cross sectional study was conducted on workers engaged in manufacturing 

 precious metal powder. Of the 27 workers, 96% had elevated urine silver 

 concentrations and 92% had elevated blood silver concentrations. Most 

 workers had symptoms of respiratory irritation and nose bleeds were 

 reported in 8 workers. Deposition of silver in the cornea of the eye was 

 detected in 5 of 8 of the long term workers. The urinary enzyme 

 N-acetyl-B-D glucosaminidase was significantly elevated in 4 individuals 

 and was correlated with blood silver concentrations and age. [Rosenman KD 

 et al; Brit J Indust Med 44 (4): 267-72 (1987)] **PEER REVIEWED** 

 It has been postulated that nickel/cobalt and nickel/palladium exhibit 

 coreactivity in patients allergic to metals. OBJECTIVES: (1) Determine the 

 incidence rate and the source for the induction of metal allergy in 3 

 groups of men: unpierced, one site pierced, and multiple sites pierced; 

 and (2) evaluate the degree of coreactivity between nickel/cobalt and 

 nickel /palladium. ... The source of the induction of the allergic 

 accounted for 5 of 6 nickel allergies and 2 of 3 gold allergies. Silver 

 jewelry was a significant predictor of an allergic response. [Enrlich A et 

 al; Am J Contact Dermat 12 (3): 151-5 (2001)] **PEER REVIEWED** 

 OBJECTIVE: Discoloration of the oral mucosa due to amalgam may appear 

 histologically merely as brown pigmentation of the fibrous extracellular 

 matrix. It was the aim of these investigations to identify the fibrous 

 component that contains silver granules. METHODS: Biopsy specimens from 

 seven patients with clinically diagnosed amalgam tattoos were investigated 

 by light and electron microscopy as well as by X-ray microanalysis. 

 RESULTS: Light microscopy revealed small brown discolored fibers in all 

 specimens; in sections stained with Weigert's resorcinfuchsin, they 

 appeared dark violet. Scanning electron microscopy revealed metallic 

 granules associated with thin fibers; by X-ray microanalysis, they 

 exhibited preferentially peaks for silver and sulfur. Transmission 

 electron microscopy detected only electron-dense particles in elastic 

 fibers. CONCLUSIONS: With the different morphological methods, silver 

 granules of amalgam tattoos were exclusively detected within elastic 

 fibers. This result indicates that granular brown discoloration of the 

 matrix fibrils is due to silver impregnation of elastic fibers. Therefore, 

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 the histopathological diagnosis of amalgam tattoo is possible even in the 

 absence of larger amalgam particles with black appearance. [Mohr W, Gorz E 

 et al; HNO 49 (6): 454-7 (2001)] **PEER REVIEWED** 

 A St. Jude Medical Silzone was implanted in a 72-year-old female, 

 suffering from mitral valve disease. Four months later, the patient had 

 acute cardiac failure due to partial detachment of the prosthetic valve. 

 The mitral annulus was ulcerated and there were multiple erosions in the 

 myocardial tissue in contact with the prosthetic valve. Histological 

 examination revealed chronic inflammation with hemosiderine deposits and 

 giant cells. No allergy to silver ions was found. The silver-coated sewing 

 cuff had caused a chronic inflammatory reaction due to a toxic reaction to 

 silver. The Silzone valve was withdrawn from the market on January 2000. 

 [Tozzi P et al; Eur J Cardiothorac Surg 19 (5): 729-31 (2001)] **PEER 

 REVIEWED** 

 Silver metal and soluble silver compounds can cause discoloration or 

 blue-grey darkening of the eyes, nose, throat, and skin. /Silver metal 

 & sol silver cmpd/ [Mackison, F. W., R. S. Stricoff, and L. J. 

 Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for 

 Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, 

 DC: U.S. Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED** 

 Potential symptoms as a result of exposure /to silver, metal, and sol cmpd 

 (as Ag)/: Blue-gray eye, nasal septum, throat, skin; irritation skin, 

 ulceration; GI. /Silver, metal, and sol cmpd (as Ag)/ [NIOSH. Pocket Guide 

 to Chemical Hazards. 5th Printing/Revision. DHHS (NIOSH) Publ. No. 85-114. 

 Washington, D.C.: U.S. Dept. of Health and Human Services, NIOSH/Supt. of 

 Documents, GPO, Sept. 1985., p. 209] **PEER REVIEWED** 

 The organs which are affected by exposure to silver, metal, and sol cmpd 

 (as Ag) are nasal septum, skin, eyes. /Silver, metal, and sol cmpd (as 

 Ag)/ [NIOSH. Pocket Guide to Chemical Hazards. 5th Printing/Revision. DHHS 

 (NIOSH) Publ. No. 85-114. Washington, D.C.: U.S. Dept. of Health and Human 

 Services, NIOSH/Supt. of Documents, GPO, Sept. 1985., p. 209] **PEER 

 REVIEWED** 

 ... DEVELOPMENT /OF ARGYRIA (POISONING BY SILVER OR A SILVER SALT WHICH 

 LEADS TO A PERMANENT ASHEN-GRAY DISCOLORATION OF THE SKIN, CONJUNCTIVA, 

 AND INTERNAL ORGANS)/ FROM INHALATION THROUGH OCCUPATIONAL EXPOSURE 

 APPEARS TO BE VERY SLOW & MAY REQUIRE YEARS. [American Conference of 

 Governmental Industrial Hygienists, Inc. Documentation of the Threshold 

 Limit Values, 4th ed., 1980. Cincinnati, Ohio: American Conference of 

 Governmmental Industrial Hygienists, Inc., 1980., p. 367] **PEER 

 REVIEWED** 

 ... A large number of case reports of argyria, mostly resulting from the 

 use of silver compounds in medical treatment by injection (silver 

 arsphenamine) or by oral admin (silver nitrate) /were examined/. /It was/ 

 concluded that the lowest total doses to produce argyria were the admin of 

 1 g of elemental silver by injection or 1.4 g after ingestion of small 

 amounts each day over several months. /Silver and silver compounds/ 

 [American Conference of Governmental Industrial Hygienists, Inc. 

 Documentation of the Threshold Limit Values and Biological Exposure 

 Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 

 1398] **PEER REVIEWED** 

 A great many case reports of argyria associated with ingestion of 

 silver-containing breath mints, antacids, & lozenges have been 

 published. Chronic use of silver-containing nose drops & topical 

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 application of silver nitrate to mucous membranes have also caused 

 argyria. Direct ocular or dermal contact with concentrated silver nitrate 

 solutions resulted in chemical burns. /Silver and silver compounds/ 

 [American Conference of Governmental Industrial Hygienists, Inc. 

 Documentation of the Threshold Limit Values and Biological Exposure 

 Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 

 1397] **PEER REVIEWED** 

 A cross-sectional study of workers producing precious-metal powder showed 

 a significant decr in creatinine clearance in those exposed to silver, 

 though this may have been due to the confounding effect of cadmium. 

 /Silver powder/ [Rom, W.N. (ed.). Environmental and Occupational Medicine. 

 2nd ed. Boston, MA: Little, Brown and Company, 1992., p. 822] **PEER 

 REVIEWED** 

 The staining of skin by silver is termed argyria and is grey-blue in 

 colour. This may be caused by a number of mechanisms such as ingestion and 

 direct implantation. We report an unusual case, caused by an impacted 

 earring, where the skin discoloration was not entirely typical of argyria. 

 This may have been due to copper impurities present in the earring. 

 [Sugden P et al; Br J Plast Surg 54 (3): 252-3 (2001)] **PEER REVIEWED** 

 In one case report of a worker who had become ill 14 hr after he had been 

 working with molten silver ingots, symptoms were limited primarily to the 

 respiratory system ... . Unfortunately, the concn and chemical comp of the 

 silver in the work room air were not known, and the history of exposure to 

 silver prior to this incident was not reported. The initial symptoms seen 

 in this patient incl audible crackles during breathing, rapid pulse, low 

 oxygen content of capillary blood, and scattered thickening of the lungs 

 observed in chest radiograms. The patient's symptoms progressed to acute 

 respiratory failure, from which the patient eventually recovered fully. 

 /Silver/ [DHHS/ATSDR; Toxicological Profile for Silver p. 13 TP-90-24 

 (1990)] **PEER REVIEWED** 

MEDICAL SURVEILLANCE: 

 Skin examination. Fecal silver level. /From Table/ [Fuscaldo, A., B. J. 

 Erlick, and B. Hindman. (eds.). Laboratory Safety-Theory and Practice. New 

 York: Academic Press, 1980., p. 267] **PEER REVIEWED** 

 Special attention should be given to other sources of silver exposure, for 

 example, medications, or previous occupational exposure. Inspection of the 

 nasal septum, eyes, and throat will generally give incidence of 

 pigmentation before generalized argyria occurs. This will usually be seen 

 first in the ear lobes, face, and hands. [Sittig, M. Handbook of Toxic and 

 Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes 

 Data Corporation, 1985., p. 789] **PEER REVIEWED** 

 Discoloration of Descemet's membrane by silver has been said to be the 

 most sensitive indicator of chronic exposure to silver, and the suggestion 

 has been made that silver workers be examined routinely with a slitlamp 

 biomicroscope for early detection of argyrosis before other manifestations 

 become evident. ... Others have reported that the initial signs of 

 occupational argyrosis were more likely to appear in the conjunctiva than 

 in the cornea. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, 

 IL: Charles C. Thomas Publisher, 1986., p. 814] **PEER REVIEWED** 

 The assessment of silver exposure can be accomplished by measurement of 

 silver. This measurement may be useful for identification of recent 

 exposure, but not for assessing chronic exposure. Whole Blood Reference 

 Ranges: Normal - Less than 5 ug/l. Exposed - Not established. Toxic - Not 

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 established. [Ryan, R.P., C.E. Terry, S.S. Leffingwell (eds.) Toxicology 

 Desk Reference 5th ed. Volumes 1-2. Taylor & Francis Philadelphia, PA. 

 2000, p. 1084] **PEER REVIEWED** 

 The literature search did not reveal reports of monitoring tests for 

 assessment of silver absorption. Serum or Plasma Reference Ranges: Normal 

 = Not established. Exposed = Not established. Toxic = Not established. 

 [Ryan, R.P., C.E. Terry, S.S. Leffingwell (eds.) Toxicology Desk Reference 

 5th ed. Volumes 1-2. Taylor & Francis Philadelphia, PA. 2000, p. 1084] 

 **PEER REVIEWED** 

 The assessment of silver exposure can be accomplished through measurement 

 of silver, which has been demonstrated to correlate well with 

 environmental exposure levels. Levels of silver in urine may be useful for 

 identification of recent exposure (in the last week or so); however, it is 

 not as useful for assessment of chronic exposure as compared to looking 

 for silver in the skin. Urine Reference Ranges: Normal - Less than 1.0 

 ug/24 hours. Exposed - Exposure to air levels from 0.27 to 60 mg/cu m 

 yielded urinary values of 5 to 261 ug/24 hour, with a mean of 27 ug/24 

 hours after a 5 day period. Toxic - Not established. [Ryan, R.P., C.E. 

 Terry, S.S. Leffingwell (eds.) Toxicology Desk Reference 5th ed. Volumes 

 1-2. Taylor & Francis Philadelphia, PA. 2000, p. 1084] **PEER 

 REVIEWED** 

 Respiratory Symptom Questionnaires: Questionnaires published by the 

 American Thoracic Society (ATS) and the British Medical Research Council 

 have proven useful for identifying people with chronic bronchitis. Certain 

 pulmonary function tests such as the FEV1 have been found to be better 

 predictors of chronic airflow obstruction. [Ryan, R.P., C.E. Terry, S.S. 

 Leffingwell (eds.) Toxicology Desk Reference 5th ed. Volumes 1-2. Taylor 

 & Francis Philadelphia, PA. 2000, p. 1085] **PEER REVIEWED** 

 Chest Radiography: Chest radiographs are widely used to assess pulmonary 

 disease. They are useful for detecting early lung cancer in asymptomatic 

 people, and especially for detecting peripheral tumors such as 

 adenocarcinomas. However, even though OSHA mandates this test for exposure 

 to some toxicants such as asbestos, experts' views on the risk to benefit 

 ratio in detection of pulmonary disease conflict, so routine annual chest 

 X-rays are not recommended for all people. [Ryan, R.P., C.E. Terry, S.S. 

 Leffingwell (eds.) Toxicology Desk Reference 5th ed. Volumes 1-2. Taylor 

 & Francis Philadelphia, PA. 2000, p. 1085] **PEER REVIEWED** 

 Pulmonary Function Tests: The tests that have been found to be practical 

 for population monitoring include: Spirometry and expiratory flow-volume 

 curves; Determination of lung volumes; Diffusing capacity for carbon 

 monoxide; Single-breath nitrogen washout; Inhalation challenge tests; 

 Serial measurements of peak expiratory flow; Exercise testing. [Ryan, 

 R.P., C.E. Terry, S.S. Leffingwell (eds.) Toxicology Desk Reference 5th 

 ed. Volumes 1-2. Taylor & Francis Philadelphia, PA. 2000, p. 1085] 

 **PEER REVIEWED** 

 The following medical procedures should be made available to each employee 

 who is exposed to silver metal & sol silver cmpd at potentially 

 hazardous levels: 1. Initial medical exam: Exam of the nasal septum, eyes, 

 and skin for evidence of pigmentation: The purpose is to establish a 

 baseline for future observations of silver deposition in tissues. 2. 

 Periodic medical exam: The aforementioned medical exam should be repeated 

 on an annual basis. /Silver metal & sol silver cmpd/ [Mackison, F. W., 

 R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational 

 Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 

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 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 

 1] **PEER REVIEWED** 

 Workers exposed to silver & silver salts should be examined routinely 

 for early signs of argyria by inspecting their eyes, nasal & buccal 

 mucosa, ear-lobes, face & hands. There are no established biologic 

 monitoring techniques for silver. /Silver and silver salts/ [Rom, W.N. 

 (ed.). Environmental and Occupational Medicine. 2nd ed. Boston, MA: 

 Little, Brown and Company, 1992., p. 823] **PEER REVIEWED** 

POPULATIONS AT SPECIAL RISK: 

 Blond people are considered more susceptible to argyria than others. 

 [Seiler, H.G., H. Sigel and A. Sigel (eds.). Handbook on the Toxicity of 

 Inorganic Compounds. New York, NY: Marcel Dekker, Inc. 1988., p. 622] 

 **PEER REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 Silver may be released from silver amalgam dental fillings when placed in 

 unlined cavities ... [Leirskar J; Scand J Dent Res 82: 74 (1974) as cited 

 in USEPA; Ambient Water Quality Criteria Doc: Silver p.C-21 (1980) EPA 

 440/5-80-071] **PEER REVIEWED** 

 Where men work with metallic silver, small particles may accidentally 

 penetrate the exposed skin. ... This may occur in occupations involving 

 the filing, drilling, hammering, turning, engraving, polishing, forging, 

 soldering & smelting of silver. [International Labour Office. 

 Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, 

 Switzerland: International Labour Office, 1983., p. 2047] **PEER 

 REVIEWED** 

 METALLIC SILVER MAY BE INHALED BY SILVER FINISHERS LEADING TO ABNORMAL 

 CHEST X-RAY FINDINGS. [Hamilton, A., and H. L. Hardy. Industrial 

 Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974., 

 p. 171] **PEER REVIEWED** 

BODY BURDEN: 

 Urine samples collected from six males, aged 28 to 51 years, who had been 

 employed in jewelry handicraft for 7 to 23 years, were analyzed for 

 silver. Urinary silver ranged from 5 to 261 micrograms per 24 hours. A 

 mean value of about 27 micrograms was found after shifts over 5 days in 

 workers performing investment casting with oxyacetylene flame, while the 

 mean urinary silver level in workers performing the electromagnetic 

 induction process was about 5 micrograms after shifts. [Minoia C et al; 

 Occupational and Environmental Chemical Hazards p.349-54 (1987)] **PEER 

 REVIEWED** 

EVIDENCE FOR CARCINOGENICITY: 

 CLASSIFICATION: D; not classifiable as to human carcinogenicity. BASIS FOR 

 CLASSIFICATION: In animals local sarcomas have been induced after 

 implantation of foils and disks of silver. However, the interpretation of 

 these findings has been questioned due to the phenomenon of solid-state 

 carcinogenesis in which even insoluble solids such as plastic have been 

 shown to result in local fibrosarcomas. ANIMAL CARCINOGENICITY DATA: 

 Inadequate . [U.S. Environmental Protection Agency's Integrated Risk 

 Information System (IRIS) on Silver (7440-22-4) Available from: 

 http://www.epa.gov/ngispgm3/iris on the Substance File List as of March 

 15, 2000] **PEER REVIEWED** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 

 Silver may be released from silver amalgam dental fillings when placed in 

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 unlined cavities ... [Leirskar J; Scand J Dent Res 82: 74 (1974) as cited 

 in USEPA; Ambient Water Quality Criteria Doc: Silver p.C-21 (1980) EPA 

 440/5-80-071] **PEER REVIEWED** 

 Where men work with metallic silver, small particles may accidentally 

 penetrate the exposed skin. ... This may occur in occupations involving 

 the filing, drilling, hammering, turning, engraving, polishing, forging, 

 soldering & smelting of silver. [International Labour Office. 

 Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, 

 Switzerland: International Labour Office, 1983., p. 2047] **PEER 

 REVIEWED** 

 METALLIC SILVER MAY BE INHALED BY SILVER FINISHERS LEADING TO ABNORMAL 

 CHEST X-RAY FINDINGS. [Hamilton, A., and H. L. Hardy. Industrial 

 Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974., 

 p. 171] **PEER REVIEWED** 

BODY BURDEN: 

 Urine samples collected from six males, aged 28 to 51 years, who had been 

 employed in jewelry handicraft for 7 to 23 years, were analyzed for 

 silver. Urinary silver ranged from 5 to 261 micrograms per 24 hours. A 

 mean value of about 27 micrograms was found after shifts over 5 days in 

 workers performing investment casting with oxyacetylene flame, while the 

 mean urinary silver level in workers performing the electromagnetic 

 induction process was about 5 micrograms after shifts. [Minoia C et al; 

 Occupational and Environmental Chemical Hazards p.349-54 (1987)] **PEER 

 REVIEWED** 

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The following information was generated from the 

Hazardous Substances Data Bank (HSDB), 

a database of the National Library of Medicine's TOXNET system 

(http://toxnet.nlm.nih.gov) on October 27, 2009. 

Query: The chemical name thallium was identified. 

The following terms were added from ChemIDplus: 

ramor 

CAS Registry Number: 7440-28-0 

1 

NAME: THALLIUM, ELEMENTAL 

RN: 7440-28-0 

NOTE: 

 This record contains information for thallium in its zero valence state 

 only. For general toxicology and environmental fate of thallium ions and 

 thallium compounds, refer to the THALLIUM COMPOUNDS record; for 

 compound-specific information, refer to the appropriate individual 

 records, e.g., dithallium sulfate, thallic oxide, etc. For information on 

 the radiological aspects of thallium and its compounds, refer to the 

 THALLIUM, RADIOACTIVE record. For general toxicological, safety and 

 handling, and environmental information on ionizing radiation emitted from 

 chemical sources including thallium, refer to the IONIZING RADIATION 

 RECORD. 

HUMAN HEALTH EFFECTS: 

HUMAN TOXICITY EXCERPTS: 

 /EPIDEMIOLOGY STUDIES/ ... Data /were presented/ on the health of workers 

 employed in a magnesium sea water battery plant; exposure to thallium was 

 in the form of fume from alloying in the furnaces, skin contact in the 

 strip-rolling of the thallium-magnesium alloy, and as a dust generated in 

 the scrap-brushing of the alloy. Some workers had exposures above 0.1 

 mg/cu m as indicated by urinary thallium concentrations of up to 236 ug/L. 

 A urine thallium concentration of 100 ug/L corresponds to a 40-hour/week 

 exposure to 0.1 mg/cu m. There were no statistically significant 

 differences in cardiovascular or gastrointestinal effects in the cohort of 

 86 exposed workers compared with 79 unexposed controls in the same 

 factory. /Thallium alloy dusts/ [American Conference of Governmental 

 Industrial Hygienists. Documentation of the TLV's and BEI's with Other 

 World Wide Occupational Exposure Values. CD-ROM Cincinnati, OH 45240-1634 

 2006.] **PEER REVIEWED** 

MEDICAL SURVEILLANCE: 

 The following medical procedures should be made available to each employee 

 who is exposed to ... thallium /and thallium/ compounds at potentially 

 hazardous levels: Initial Medical Examination: A complete history and 

 physical examination: The purpose is to detect existing conditions that 

 might place the exposed employee at increased risk, and to establish a 

 baseline for future health monitoring. Examination of the eyes, nervous 

 system, lung, liver, kidneys, gastrointestinal tract, and body hair should 

 be stressed. Urinalysis: Since kidney damage has been observed in humans 

 exposed to thallium, a urinalysis should be obtained to include at a 

 minimum specific gravity, albumin, glucose, and a microscopic 

 /examination/ on centrifuged sediment. Periodic Medical Examination: These 

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 medical examinations should be repeated on an annual basis. /Thallium and 

 thallium compounds/ [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, 

 Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical 

 Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. 

 Government Printing Office, Jan. 1981., p. 1] **PEER REVIEWED** 

 Respiratory Symptom Questionnaires: Questionnaires have been published by 

 the American Thoracic Society and the British Medical Research Council. 

 These questionnaires have been found to be useful in identification of 

 people with chronic bronchitis, however certain pulmonary function tests 

 such as FEV 1 ... have been found to be better predictors of chronic 

 airflow obstruction. /Thallium/ [Ryan, R.P., C.E. Terry (eds.). Toxicology 

 Desk Reference 4th ed. Volumes 1-3. Taylor & Francis, Washington, 

 D.C. 1997., p. 2126] **PEER REVIEWED** 

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