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EC number: 215-572-9
CAS number: 1332-65-6
In vitro data
bacterial reverse mutation assay (e.g. Ames test) (gene mutation)
Salmonella typhimurium Strains TA98, TA100, TA1535, TA1537, TA102 (met. act.: with and without)
Doses: 1.6, 8, 40, 200, 1000 µg/plate and 50, 100, 200, 400, 800 µg/plate in mutation experiments 1 and 2, respectively.
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Evaluation of results:
negative for Salmonella typhimurium Strains TA98, TA100, TA1535, TA1537, TA102(all strains/cell types tested); met. act.: with and without; cytotoxicity: yes (See additional information on results.)
1 (reliable without restriction)
Test material (common name): Cu2+ as copper sulphate pentahydrate
Ballantyne, M. (1994)
The existence of two negative in vivo studies (summarised below) negates
the need for in vitro mammalian cell assays.
Under normal physiological conditions, the concentration of free copper
is extremely low in vivo and the majority of the copper is bound to
ceruplasmin and albumin. In addition, cells contain
high concentrations of potent antioxidants (e.g. glutathione). Therefore,
the biological relevance of any in vitro observations would be uncertain
where high concentration of the free ion would be available in cell
culture growth medium. From reviews of public domain
data (WHO, 1998; VRAR, 2008), there is conflicting evidence regarding
the activity of copper in cell based assays for genotoxicity, however,
due to the relevance of such studies in determining the genotoxicity
potential of copper it is considered not appropriate or applicable to
use these studies for copper and copper compounds.
In addition, due to the inappropriate level of free cupric ion present
in any in vitro assays, the results of such studies will also be
affected by the toxicity of the cupric ion to the mammalian cell lines.
Therefore it was considered more appropriate to review the genotoxic
potential of copper and copper compounds using in vivo studies.
unscheduled DNA synthesis (DNA damage and/or repair)
rat (Wistar) male
632.5 or 2000 mg/kg (actual ingested)
equivalent or similar to OECD Guideline 486 (Unscheduled DNA Synthesis (UDS) Test with Mammalian Liver Cells in vivo)
Evaluation of results: negative
Genotoxicity: negative (male); toxicity: not examined
Test material (common name):Cu2+ as copper sulphate pentahydrate
Ward, P.J. (1994)
mouse (CD-1) male/female
EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test) (Cited as Directive 2000/32/EC, B.12)
Genotoxicity: negative (male/female)
Riley, S.E. (1994)
There are additional equivocal in vivo genotoxicity studies in the
public domain. However these studies do not adhere
fully to OECD guidelines, have unreliable routes of administration (i.v)
and are not conducted to GLP. When toxicity studies
are conducted with either i.p. and i.v. routes of administration, they
bypass the normal uptake and distribution mechanism that is specifically
designed to protect the animal from the toxic/reactive Cu2+ ion. This
invalidates these studies from regulatory decision-making procedures
where the normal production and use of the chemical would not result in
direct i.v. or i.p. exposure.
Therefore, these studies have been given lower quality criteria than
those summarised above and should not be used for either risk assessment
purposes or to classify copper compounds. However, the VRAR, 2008
provides a full review of these studies and the discussion on the
unsuitability/unacceptability of these studies.
From the results above, copper sulphate pentahydrate, copper and other
copper compounds are not considered genotoxic.
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