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Toxicological information

Carcinogenicity

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Description of key information

Data from experimental studies clearly indicates that cadmium is an animal carcinogen. Only one study reported an increase in cancer after oral exposure to soluble cadmium compounds. However, strong evidence exists that inhalation of cadmium oxide dust and fumes or cadmium chloride causes lung cancer in rat. Mice exposed to equivalent levels of cadmium oxide had only marginally significant elevations in lung cancer and no evidence for lung carcinogenicity was found in hamster, so that it has been suggested that interspecies and also inter-strain differences may play a role in the sensitivity to cadmium-induced carcinogenesis. Intrathoracic, intratracheal and subcutaneous exposure to cadmium compounds have also been shown to produce carcinogenic responses in rat.
Overall, there is currently no conclusive evidence from human studies that cadmium acts as a carcinogen following oral exposure. In worker populations exposed via inhalation, a statistically significant increase in mortality from lung cancer was initially reported but this has not been supported in later studies. More recent analyses suggest that measures protecting against renal/respiratory effects should also be protective of lung cancer.
Conclusive data is not available for all forms of cadmium but the weight of evidence collected from mutagenicity tests, long-term animal studies and epidemiological studies leads to conclude that cadmium oxide should be considered at least as a suspected human carcinogen (lung cancer). Cadmium metal is a carcinogen when injected in experimental animals. No studies exist for the metal in humans or animals, which does not allow to sufficiently document its carcinogenic potential.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Dose descriptor:
LOAEL
3.5 mg/kg bw/day

Carcinogenicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LOAEC
0.03 mg/m³

Additional information

Data from experimental studies clearly indicates that cadmium is an animal carcinogen. Only one study reported an increase in cancer after oral exposure to soluble cadmium compounds. However, strong evidence exists that inhalation of cadmium oxide dust and fumes or cadmium chloride causes lung cancer in rat. Mice exposed to equivalent levels of cadmium oxide had only marginally significant elevations in lung cancer and no evidence for lung carcinogenicity was found in hamster, so that it has been suggested that interspecies and also inter-strain differences may play a role in the sensitivity to cadmium-induced carcinogenesis. Intrathoracic, intratracheal and subcutaneous exposure to cadmium compounds have also been shown to produce carcinogenic responses in rat.

Overall, there is currently no conclusive evidence from human studies that cadmium acts as a carcinogen following oral exposure. In worker populations exposed via inhalation, a statistically significant increase in mortality from lung cancer was initially reported but this has not been supported in later studies. More recent analyses suggest that measures protecting against renal/respiratory effects should also be protective of lung cancer.

Conclusive data is not available for all forms of cadmium but the weight of evidence collected from mutagenicity tests, long-term animal studies and epidemiological studies leads to conclude that cadmium oxide should be considered at least as a suspected human carcinogen (lung cancer). Cadmium metal is a carcinogen when injected in experimental animals. No studies exist for the metal in humans or animals, which does not allow to sufficiently document its carcinogenic potential.

Following long discussions, cadmium oxide was classified by the CMR Working Group as Carc. Cat. 2; R45 (may cause cancer), i.e. carcinogenic potential irrespective of the exposure route [1] and appears as such in Annex I of Directive 67/548/EC (the corresponding GHS-CLP classification would be Carcinogenic category 1B; H350). Cadmium sulphate, cadmium chloride and cadmium metal have been granted the same classification, based on weight of evidence and read-across. By analogy, a comparable classification could be considered for the other highly and slightly soluble cadmium compounds (e.g. cadmium nitrate, hydroxide and carbonate).

Apart from cadmium sulphide, none of the insoluble cadmium compounds (e.g. cadmium sulfoselenide, cadmium zinc sulphide or cadmium telluride), not expected to penetrate easily into the organisms, are classified for carcinogenicity. Cadmium sulphide is an exception. As there is no stong evidence to specifically support its Carc. Cat. 2; R45 classification, a revision of the classification may be appropriate based on solubility properties.


[1] Although there is evidence that cadmium may cause lung cancer after inhalation exposure, there is no indication for a carcinogenic potential in the general population after oral exposure. A classification as Carc. Cat. 2: R49, i.e. may cause cancer by inhalation, could have been envisaged.



Carcinogenicity: via oral route (target organ): urogenital: prostate

Carcinogenicity: via inhalation route (target organ): respiratory: lung

Justification for classification or non-classification

Following long discussions, cadmium oxide was classified by the CMR Working Group as Carc. Cat. 2; R45 (may cause cancer), i.e. carcinogenic potential irrespective of the exposure route [1] and appears as such in Annex I of Directive 67/548/EC (the corresponding GHS-CLP classification would be Carcinogenic category 1B; H350). Cadmium sulphate, cadmium chloride and cadmium metal have been granted the same classification, based on weight of evidence and read-across. By analogy, a comparable classification could be considered for the other highly and slightly soluble cadmium compounds (e.g. cadmium nitrate, hydroxide and carbonate).

Apart from cadmium sulphide, none of the insoluble cadmium compounds (e.g. cadmium sulfoselenide, cadmium zinc sulphide or cadmium telluride), not expected to penetrate easily into the organisms, are classified for carcinogenicity. Cadmium sulphide is an exception. As there is no strong evidence to specifically support its Carc. Cat. 2; R45 classification, a revision of the classification may be appropriate based on solubility properties.


[1] Although there is evidence that cadmium may cause lung cancer after inhalation exposure, there is no indication for a carcinogenic potential in the general population after oral exposure. A classification as Carc. Cat. 2: R49, i.e. may cause cancer by inhalation, could have been envisaged.