Search tips
Search criteria 


Logo of envhperEnvironmental Health PerspectivesBrowse ArticlesAbout EHPGeneral InformationAuthorsMediaProgramsPartnerships
Environ Health Perspect. 1981 August; 40: 83–91.
PMCID: PMC1568838
Research Article

Bioassay of metals for carcinogenesis: whole animals.


Metals have been evaluated as potential carcinogens by administering pure elements or compounds by a large variety of routes. These include mixing the agent in the food, dissolving the test compound in the drinking water, or administering the material by gavage. The respiratory tract routes tested include inhalation, intratracheal instillation, the direct injection of particulates into the pleural cavity, or the implantation of hooks by surgical intervention. The parenteral routes used were intravenous injection, intraperitoneal injection, subcutaneous implantation, as well as intrafemoral and intramuscular injection. This latter route is the most commonly used. There are major objections to the subcutaneous implantations route, and data generated from these experiments are difficult to interpret for the foreign body reaction may give rise also to fibrosarcomas. This then is a nonspecific reaction. Exotic routes tested include intrarenal, intratesticular, and intracranial injections. The endpoints of the carcinogenic reactions are, in the main, sarcomas of certain types with fibrosarcomas predominating. Rhabdomyosarcomas are the next most frequent cancer found, and squamous cell carcinoma may account for less than 2% of the cancers reported. Much more research is necessary to clarify the nature of metal carcinogenesis. Dose-response information is almost nonexistent; the divided dose problem has not been studied adequately, and very little information is available on interspecies reactions. More work is needed to help interpret the mechanism of action.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.7M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Sunderman JW., Jr A review of the carcinogenicities of nickel, chromium and arsenic compounds in man and animals. Prev Med. 1976 Jun;5(2):279–294. [PubMed]
  • Sunderman FW., Jr Metal carcinogenesis in experimental animals. Food Cosmet Toxicol. 1971 Feb;9(1):105–120. [PubMed]
  • Sunderman FW., Jr Carcinogenic effects of metals. Fed Proc. 1978 Jan;37(1):40–46. [PubMed]
  • Furst A, Haro RT. A survey of metal carcinogenesis. Prog Exp Tumor Res. 1969;12:102–133. [PubMed]
  • Furst A. Tumorigenic effect of an organomanganese compound on F344 rats and Swiss albino mice. J Natl Cancer Inst. 1978 May;60(5):1171–1173. [PubMed]
  • O'Gara RW, Brown JM. Comparison of the carcinogenic actions of subcutaneous implants of iron and aluminum in rodents. J Natl Cancer Inst. 1967 Jun;38(6):947–957. [PubMed]
  • OPPENHEIMER BS, OPPENHEIMER ET, DANISHEFSKY I, STOUT AP. Carcinogenic effect of metals in rodents. Cancer Res. 1956 Jun;16(5):439–441. [PubMed]
  • Bryson G, Bischoff F. The limitations of safety testing. Prog Exp Tumor Res. 1969;11:100–133. [PubMed]
  • Furst A, Schlauder M, Sasmore DP. Tumorigenic activity of lead chromate. Cancer Res. 1976 May;36(5):1779–1783. [PubMed]
  • Preussmann R, Ivankovic S. Absence of carcinogenic activity in BD rats after oral administration of high doses of bismuth oxychloride. Food Cosmet Toxicol. 1975 Oct;13(5):543–544. [PubMed]
  • Kroes R, van Logten MJ, Berkvens JM, de Vries T, van Esch GJ. Study on the carcinogenicity of lead arsenate and sodium arsenate and on the possible synergistic effect of diethylnitrosamine. Food Cosmet Toxicol. 1974 Oct;12(5-6):671–679. [PubMed]
  • Roe FJ, Boyland E, Millican K. Effects of oral administration of two tin compounds to rats over prolonged periods. Food Cosmet Toxicol. 1965 Aug;3(2):277–280. [PubMed]
  • BOYLAND E, DUKES CE, GROVER PL, MITCHLEY BC. The induction of renal tumors by feeding lead acetate to rats. Br J Cancer. 1962 Jun;16:283–288. [PubMed]
  • van ESCH G, van GENDEREN, VINK HH. The induction of renal tumours by feeding of basic lead acetate to rats. Br J Cancer. 1962 Jun;16:289–297. [PubMed]
  • Van Esch GJ, Kroes R. The induction of renal tumours by feeding basic lead acetate to mice and hamsters. Br J Cancer. 1969 Dec;23(4):765–771. [PubMed]
  • Schroeder HA, Mitchener M. Scandium, chromium(VI), gallium, yttrium, rhodium, palladium, indium in mice: effects on growth and life span. J Nutr. 1971 Oct;101(10):1431–1437. [PubMed]
  • Schroeder HA, Mitchener M. Selenium and tellurium in rats: effect on growth, survival and tumors. J Nutr. 1971 Nov;101(11):1531–1540. [PubMed]
  • Brain JD, Valberg PA. Deposition of aerosol in the respiratory tract. Am Rev Respir Dis. 1979 Dec;120(6):1325–1373. [PubMed]
  • HUEPER WC. Experimental studies in metal cancerigenesis. IX. Pulmonary lesions in guinea pigs and rats exposed to prolonged inhalation of powdered metallic nickel. AMA Arch Pathol. 1958 Jun;65(6):600–607. [PubMed]
  • Saknyn' AV, Blokhin VA. O razvitii zlokachestvennykh opukholei u krys pod vliianiem nikel'soderzhashchikh érozolei. Vopr Onkol. 1978;24(4):44–48. [PubMed]
  • Wehner AP, Busch RH, Olson RJ, Craig DK. Chronic inhalation of nickel oxide and cigarette smoke by hamsters. Am Ind Hyg Assoc J. 1975 Nov;36(11):801–810. [PubMed]
  • Ottolenghi AD, Haseman JK, Payne WW, Falk HL, MacFarland HN. Inhalation studies of nickel sulfide in pulmonary carcinogenesis of rats. J Natl Cancer Inst. 1975 May;54(5):1165–1172. [PubMed]
  • Wagner WD, Groth DH, Holtz JL, Madden GE, Stokinger HE. Comparative chronic inhalation toxicity of beryllium ores, bertrandite and beryl, with production of pulmonary tumors by beryl. Toxicol Appl Pharmacol. 1969 Jul;15:10–29. [PubMed]
  • Sanders CL, Cannon WC, Powers GJ. Lung carcinogenesis induced by inhaled high-fired oxides of beryllium and plutonium. Health Phys. 1978 Aug;35(2):193–199. [PubMed]
  • Bischoff F, Bryson G. Toxicologic studies of tin needles at the intrathoracic site of mice. Res Commun Chem Pathol Pharmacol. 1976 Oct;15(2):331–340. [PubMed]
  • Saffiotti U, Montesano R, Sellakumar AR, Cefis F, Kaufman DG. Respiratory tract carcinogenesis in hamsters induced by different numbers of administrations of benzo(a)pyrene and ferric oxide. Cancer Res. 1972 May;32(5):1073–1081. [PubMed]
  • Ho W, Furst A. Intratracheal instillation method for mouse lungs. Oncology. 1973;27(5):385–393. [PubMed]
  • Kasprzak KS, Marchow L, Breborowicz J. Pathological reactions in rat lungs following intratracheal injection of nickel subsulfide and 3,4-benzpyrene. Res Commun Chem Pathol Pharmacol. 1973 Jul;6(1):237–245. [PubMed]
  • Lane BP, Mass MJ. Carcinogenicity and cocarcinogenicity of chromium carbonyl in heterotopic tracheal grafts. Cancer Res. 1977 May;37(5):1476–1479. [PubMed]
  • Lau TJ, Hackett RL, Sunderman FW., Jr The carcinogenicity of intravenous nickel carbonyl in rats. Cancer Res. 1972 Oct;32(10):2253–2258. [PubMed]
  • Stoner GD, Shimkin MB, Troxell MC, Thompson TL, Terry LS. Test for carcinogenicity of metallic compounds by the pulmonary tumor response in strain A mice. Cancer Res. 1976 May;36(5):1744–1747. [PubMed]
  • Ball RA, Van Gelder G, Green JW, Jr, Reece WO. Neoplastic sequelae following subcutaneous implantation of mice with rare earth metals. Proc Soc Exp Biol Med. 1970 Nov;135(2):426–430. [PubMed]
  • Shabaan AA, Marks V, Lancaster MC, Dufeu GN. Fibrosarcomas induced by cobalt chloride (CoCl2) in rats. Lab Anim. 1977 Jan;11(1):43–46. [PubMed]
  • GILMAN JP. Metal carcinogenesis. II. A study on the carcinogenic activity of cobalt, copper, iron, and nickel compounds. Cancer Res. 1962 Feb;22:158–162. [PubMed]
  • Kazantzis G, Hanbury WJ. The induction of sarcoma in the rat by cadmium sulphide and by cadmium oxide. Br J Cancer. 1966 Mar;20(1):190–199. [PubMed]
  • HUEPER WC. Experimental studies in metal cancerigenesis. IV. Cancer produced by parenterally introduced metallic nickel. J Natl Cancer Inst. 1955 Aug;16(1):55–73. [PubMed]
  • Mazabraud A. Production expérimentale de sarcomes osseux chez le lapin par injection unique locale de Béryllium. Bull Cancer. 1975 Jan-Mar;62(1):49–58. [PubMed]
  • RIVIERE MR, CHOUROULINKOV I, GUERIN M. [Tumors of the testicle in the rat after injection of zinc chloride]. C R Hebd Seances Acad Sci. 1959 Dec 9;249:2649–2651. [PubMed]
  • Damjanov I, Sunderman FW, Jr, Mitchell JM, Allpass PR. Induction of testicular sarcomas in Fischer rats by intratesticular injection of nickel subsulfide. Cancer Res. 1978 Feb;38(2):268–276. [PubMed]
  • Sosiński E. Morphological changes in rat brain and skeletal muscle in the region of nickel oxide implantation. Neuropatol Pol. 1975 Jul-Dec;13(3-4):479–483. [PubMed]
  • Rencher AC, Carter MW, McKee DW. A retrospective epidemiological study of mortality at a large western copper smelter. J Occup Med. 1977 Nov;19(11):754–758. [PubMed]
  • Ohsaki Y, Abe S, Kimura K, Tsuneta Y, Mikami H, Murao M. Lung cancer in Japanese chromate workers. Thorax. 1978 Jun;33(3):372–374. [PMC free article] [PubMed]
  • Berg JW, Burbank F. Correlations between carcinogenic trace metals in water supplies and cancer mortality. Ann N Y Acad Sci. 1972 Jun 28;199:249–264. [PubMed]
  • Crouch E, Wilson R. Interspecies comparison of carcionogenic potency. J Toxicol Environ Health. 1979 Nov;5(6):1095–1118. [PubMed]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Science