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 

### Page 1 of 3

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtPATTERNS 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 

### Page 2 of 3

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtEXPOSURE 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** 

### Page 3 of 3

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThe 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: 

### Page 1 of 3

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txthttp://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 

### Page 2 of 3

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtinorganic 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** 

### Page 3 of 3

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThe 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 

### Page 1 of 5

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtcauses 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThe 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 

### Page 3 of 5

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt20% 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 

### Page 4 of 5

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtexposure 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThe 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtchronic 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtto 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtDISCHARGE. 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txthygiene 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtAcute 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtcancer. 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtinitial 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 

### Page 8 of 16

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtcompounds/ [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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtIn 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtCONFIRMED 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtdisease. 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtOSHA 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtberyllium (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: 

### Page 14 of 16

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtBeryllium 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtBODY 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThe 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtpoison ... [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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThe 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtCadmium 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtto 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtresult 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtbe 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtpopulation 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtREVIEWED**

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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtJr., 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThe 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtblood 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtEffects 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThe 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt/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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt/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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtLung 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtpneumothorax. 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt3.31 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtreplacements. [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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtsmoking 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 

### Page 8 of 14

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt(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 

### Page 9 of 14

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtor 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; 

### Page 10 of 14

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt/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 

### Page 11 of 14

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtvalues 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 

### Page 12 of 14

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtexposure 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. 

### Page 13 of 14

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtGovernment 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** 

### Page 14 of 14

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThe 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** 

### Page 1 of 9

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtFumes 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 

### Page 2 of 9

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtappetite, 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, 

### Page 3 of 9

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtCONSISTING 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 

### Page 4 of 9

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtthat 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** 

### Page 5 of 9

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThe 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 

### Page 6 of 9

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtToxicology. 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** 

### Page 7 of 9

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtSTUDY 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/ 

### Page 8 of 9

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt[WHO; Environ Health Criteria 200: Copper p.148 (1998)] **PEER REVIEWED** 

### Page 9 of 9

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThe 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 

### Page 1 of 8

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtIF 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 

### Page 2 of 8

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtgroup. 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtdeposition 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtdentine 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 

### Page 5 of 8

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txthalf-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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtSRP: 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 

### Page 7 of 8

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtLEAD 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThe 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 

### Page 1 of 12

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtgastroenteritis 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txttoxicity. 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtAMONG 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtconcentration 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 

### Page 5 of 12

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txttremors, 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 

### Page 6 of 12

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtnot 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtRespiratory 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtWayland 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 

### Page 9 of 12

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtlaboratory 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 

### Page 10 of 12

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtProtection 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 

### Page 11 of 12

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtMERCURY 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThe 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt/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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtand 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 

### Page 3 of 4

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtChemicals 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** 

### Page 4 of 4

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThe 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 

### Page 1 of 10

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtexcretion 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 

### Page 2 of 10

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtcarbonyl, 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtMetals. 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtairborne 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtcoating, 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtJ.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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtPROBABLE 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 

### Page 8 of 10

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtviability 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 

### Page 9 of 10

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtexperimental 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** 

### Page 10 of 10

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThe 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 

### Page 1 of 5

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtevidence 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtdose 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtPSYCHONEUROTIC 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtmay 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThe 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtA 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt10 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtthe 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtapplication 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtestablished. [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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txt(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 

### Page 7 of 8

10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtunlined 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtThe 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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10/27/2009 htt p ://toxnet.nlm.nih. g ov/c g i- b in/sis/download.txtmedical 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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