The mutagenic and carcinogenic effects of cadmium: An update†

Publisher Website
Google Scholar
Abstract
Cadmium has given conflicting results in tests for mutagenic activity. Gene mutation studies in bacteria and yeasts have been inconclusive, while rec‐assay has elicited a weak mutagenic response. Chromosomal aberrations were not observed in bone marrow cells of rodents treated with cadmium salts. Neither dominant lethal mutations nor heritable translocations have been seen. Observations on chromosomal aberrations following occupational exposure to cadmium have been conflicting. However in these studies mixed exposures had occurred. There is some evidence that cadmium interferes with spindle formation in mice and hamsters. Some of the positive results have been observed at borderline cytotoxic concentrations of cadmium suggesting that the mutagenic effect observed may have been an indirect one. A number of cadmium compounds have given rise to sarcoma following subcutaneous or intramuscular injection in rodents. In sufficient dosage, destruction of testicular tissue has been followed by interstitial cell hyperplasia and this has been interpreted by some as neoplasia. The inhalation by Wistar rats of a cadmium chloride aerosol at concentrations within the TLV for cadmium gave rise to a high incidence of primary lung cancer with a dose response relationship.33 The induction of lung cancer provides the only convincing evidence for a possible carcinogenic role for cadmium in experimental studies other than at a site of injection and the confirmation of these findings and their extension to other cadmium compounds is awaited. Epidemiologic studies on the carcinogenic effects of exposure to cadmium compounds have also to date given inconclusive results. The earlier findings of an excess mortality from prostatic cancer has not been confirmed in later studies. Doll41 considered that cadmium should cease to be regarded as a prostatic carcinogen, although Elinder et al.40 by combining the data from six different cohorts concluded that high past exposure, above 0.3mgCd/m3, supported an association between prostatic cancer and exposure to cadmium. Small increases in lung cancer mortality in cadmium exposed workers have been reported by a number of investigators, with a greater than twofold excess risk in cadmium smelter workers observed by Thun et al.45 Although these investigators considered that cigarette smoking and exposure to arsenic could not have caused their observed excess lung cancer risk, in all these studies the problem of the confounding factors, cigarette smoking and exposure to other putative environmental carcinogens, remains. In our own cohort mortality study no excess prostatic cancer was found.38 In a case control study taken from this and from two other British cohorts, marginally increased risks were observed for prostatic cancer after high or medium past exposure but these were not statistically significant.39 A five year follow up of the initial cohort study now nearing completion confirms no excess mortality from prostatic cancer. In our initial cohort study a significant excess risk from lung cancer was found in men with more than 10 years employment, but only in the low exposure category. The five year update confirms this excess and reveals also an increased risk from stomach cancer. As more than one half of the total study population had been employed in a lead‐zinc‐cadmium smelter, a further case control study for lung cancer was performed, using a matched logistic regression technique which took account of six exposure variables.50 An excess lung cancer risk was shown related to length of employment in the smelter, but this excess risk could not be shown to be related to past cadmium exposure. While there is some evidence to suggest that exposure to cadmium may cause lung cancer and possibly stomach cancer, this evidence is as yet not conclusive. In future epidemiologic studies confounding factors, in particular the role of multiple exposures will require careful study.