Registration Dossier

Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
genetic toxicity in vivo
Remarks:
Type of genotoxicity: other: chromosome and genome mutations
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The Scientific Committee on Occupational Exposure Limits (SCOEL) is is a committee of the European Commission.

Data source

Reference
Reference Type:
review article or handbook
Title:
Recommendation from the Scientific Committee on Occupational Exposure Limits for Copper and its inorganic compounds. SCOEL/SUM/171 March 2013
Author:
SCOEL
Year:
2013
Bibliographic source:
Scientific Committee on Occupational Exposure Limits; DRAFT for consultation March-September 2013. Employment, Social Affairs & Inclusion (EC); Ref. Ares(2013)340506 - 15/03/2013

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The evaluation is based on the results of in vivo studies in mice.
GLP compliance:
not specified
Remarks:
not applicable (it is a review)
Type of assay:
other: chromosome aberration assay and micronucleus tests

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Copper

Results and discussion

Test resultsopen allclose all
Sex:
not specified
Genotoxicity:
positive
Remarks:
chromosomal aberrations (chromatid type) and increase of chromosomal breaks at 1.1–6.6 mg Cu/kg bw in Albino mice
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Sex:
not specified
Genotoxicity:
positive
Remarks:
chromosomal aberrations (chromatide gaps) in Swiss mice at 1.3–5 mg Cu/kg bw (i.p given as a single dose or in five daily doses; oral or s.c.); increase in micronuclei (i.p)
Toxicity:
yes
Remarks:
there were signs of cytotoxic effects at all doses.
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
not examined
Sex:
not specified
Genotoxicity:
positive
Remarks:
increased rate of micronuclei in BALB/c mice (twice i. p. at 14-hour intervals)
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Sex:
male/female
Genotoxicity:
positive
Remarks:
micronuclei in bone marrow cells of CF1 mice gavaged for six consecutive days
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Sex:
male
Genotoxicity:
positive
Remarks:
DNA single-strand breaks by the comet assay in leukocytes from Swiss albino mice (oral, 4.9 mg Cu/kg bw)
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Sex:
male/female
Genotoxicity:
positive
Remarks:
DNA single-strand breaks, detected by the comet assay; induced in blood cells of Swiss Webster mice (oral)
Toxicity:
not specified
Vehicle controls validity:
not specified
Negative controls validity:
not specified
Positive controls validity:
not specified
Sex:
not specified
Genotoxicity:
negative
Remarks:
no increase in micronuclei in CBA mice exposed to single i.p. dose of 1.7–5.1 mg Cu/kg bw (copper sulphate pentahydrate)
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Single intraperitoneal injection of copper sulphate pentahydrate to Albino mice induced a significant and dose-related increase in chromosomal aberrations (chromatid type) at doses of 1.1–6.6 mg Cu/kg bw. There was also an increase of chromosomal breaks at the highest dose (Agarwal et al 1990).

A study by Bhunya and Pati (1987) reported an increase in chromosomal aberrations (chromatide gaps) in Swiss mice, which were intraperitoneally injected in single doses of 1.3–5 mg Cu/kg bw as copper sulphate, either given as a single dose or in five daily doses. Further studies were carried out with single doses of 5.1 mg Cu/kg bw by the oral or subcutaneous route. All exposures resulted in significant increases in chromosomal aberrations. In the mice dosed once intraperitoneally, the effect was dose-dependent. In parallel studies with the same strain of mice, these authors also reported a significant and dose-dependent increase in the incidence of micronuclei after two intraperitoneal injections (24 hours apart) of doses of 1.3–5 mg Cu/kg bw and day as copper sulphate. The authors used no positive controls and there were signs of cytotoxic effects at all doses.

A significant and dose-dependently increased rate of micronuclei was also reported in a study by Rusov et al (1997). These authors exposed BALB/c mice twice intraperitoneally at 14-hour intervals to copper acetate at doses of 0.3–13.0 mg Cu/kg bw. Male and female CF1 mice were gavaged for six consecutive days with CuSO4 (8.25 mg Cu/kg bw and day). This dose regimen induced micronuclei in bone marrow cells and was genotoxic when evaluated in the neutral and the alkaline version of the comet assay in whole blood (Prá et al 2008). Data on cytotoxic effects on bone marrow were not given. Saleha et al (2004) also detected DNA single-strand breaks by the comet assay in leukocytes from male Swiss albino mice administered orally up to 4.9 mg Cu/kg bw as copper sulphate. The trypan blue exclusion technique showed a cell viability ranging from 90–95 %. DNA single-strand breaks, detected by the comet assay (Franke et al 2006), were also induced in blood cells from male and female Swiss Webster mice after oral administration of copper sulphate (8.50 Cu mg/kg bw). In contrast to these findings, Tinwell and Ashby (1990) did not observe an increase in micronuclei following a single intraperitoneal injection of copper sulphate pentahydrate at doses of 1.7–5.1 mg Cu/kg bw to CBA mice.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): ambiguous
Copper sulphate (degree of hydratation is not specified) induced chromosomal aberrations, breaks and increase in micronuclei in mice of different strains, while inconsistent data are available on copper sulphate pentahydrate.
Executive summary:

Copper sulphate compounds (degree of hydratation is not specified) induced chromosomal aberrations, breaks and increase in micronuclei in mice of different strains. On contrary, copper sulphate pentahydrate induced an increase in chromosomal aberrations (chromatid type) and chromosomal breaks in Albino mice treated intraperitoneally, while no increase in micronuclei following a single intraperitoneal injection was observed in CBA mice.