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EC number: 244-168-5
CAS number: 21041-95-2
Data from in vitro and in vivo
experimental systems are not consistent but suggests that cadmium, in
certain forms, has mutagenic properties. With regard to human exposure,
data are also conflicting but again a mutagenic potential both via oral
and inhalation exposure routes cannot be excluded.
Different possible non-mutually
exclusive direct and indirect mechanisms of mutagenicity have been
identified in vitro, although their relevance toin vivosituations
is not clearly established. A recent review by Parry and Parry (2009)
(available in IUCLID 5 under ‘7.12 Additional toxicological
information’) concluded that there is considerable evidence to suggest
that the primary mechanism of genotoxicity is the production of
oxidative lesions. In this case, there could be a threshold at
low doses where the DNA repair enzymes remove the lesions, thus reducing
the potential for genetic changes in cells. The EU Risk Assessment
Report (RAR) (ECB, 2007) states that most of the mechanisms
proposed to explain the mutagenicity of cadmium ions are dose-dependent
and support the possibility of a threshold for mutagenic effects (Madle et
al., 2000; Kirsch-Volders et al., 2000). Further research may
be able to determine No Adverse Effect Levels (NOAEL) and generate
It should however be noted that
cadmium has also been suggested to act as a co-mutagen rather than as a
mutagen, e.g. by decreasing fidelity in DNA synthesis or interfering
with DNA repair mechanisms (Schwerdtle et al., 2010). In this
case, repair activity within a potential thresholded region of the
dose-response-curve would be limited (Parry and Parry, 2009).
If cadmium inhibits the repair of DNA
damage induced by other agents, this could explain some of the
differences in the results of cytogenetic studies in human populations.
Indeed, chromosome aberrations might be increased in the different
populations/subjects with different additional
occupational/environmental exposures as a result of unrepaired damage
The study of Forni et al.(1990;
1992), is cited in SCOEL (2010), for referring to the 10 µg/g creatinin
in Cd/urine as a threshold for genotoxicity. SCOEL also published (draft
note on the 76thmeeting, March 2010) that ‘having defined a
threshold for genotoxicity, it was shown that renal and respiratory
effects are more sensitive than genotoxicity, in turn thought to be a
pre-requisite for carcinogenicity’.
Based upon the available evidence at
present it is concluded that cadmium has a threshold for genotoxicity. A
second important conclusion is that the renal respiratory effects are
more sensitive than the genotoxic effects. The risk management for
cadmium consequently is based on the protection for renal and inhalatory
Based on available data and
read-across, cadmium chloride and sulphate are currently classified as Muta.
Cat. 2; R46 (may cause heritable genetic damage)in Annex I of
Directive 67/548/EC(the corresponding GHS-CLP classification would be Mutagenic
category 1B; H340). By analogy, the other highly soluble forms of
cadmium (i.e. cadmium nitrate) warrant comparable classifications.
At present, the slightly soluble
cadmium metal and oxide are classified as Muta. Cat. 3; R68 (possible
risk of irreversible effects) in Annex I of Directive 67/548/EC (the
corresponding GHS-CLP classification would be Mutagenic category 2;
H341). A similar classification for cadmium hydroxide and carbonate
may therefore be considered.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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