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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro transformation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
Cytotoxic and neoplastic transforming effects of industrial hexavalent chromium pigments in Syrian hamster embryo cells.
Author:
Elias Z, Poirot O, Pezerat H, Suquet H, Schneider O, Daniere MC, Terzetti F, Baruthio F, Fournier M, Cavelier C
Year:
1989
Bibliographic source:
Carcinogenesis 10 (11) 2043-52

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EU Method B.21 (In Vitro Mammalian Cell Transformation Test)
GLP compliance:
no
Type of assay:
in vitro mammalian cell transformation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
The chemical composition of zinc potassium chromate: 20.9-23.6% Cr, 29.7-30.3% Zn, and 5.4-9.1% K

Method

Species / strain
Species / strain:
other: Syrian hamster embryo cells
Metabolic activation:
without
Vehicle:
Dulbecco's MEM, pH7.2
Controls
Negative controls:
no
Solvent controls:
no
True negative controls:
no
Positive controls:
no
Details on test system and conditions:
METHOD OF APPLICATION: in medium
DURATION
- Preincubation period: 24 h
- Exposure duration: 7 days
- Expression time (cells in growth medium): -
- Selection time (if incubation with a selection agent): -
- Fixation time (start of exposure up to fixation or harvest of cells): 7 days
DETERMINATION OF CYTOTOXICITY
- Method: Inhibition of cell growth.
Evaluation criteria:
The criteria decribed by DiPaolo (Journal Natl Cancer Inst, 42, 867-876, 1969) and Pienta et al. (Short term tests for Chemical carcinogens, ed. H.F. Stick and R.H.C. San, Springer-Verlag, NY, p. 323-337, 1981) was used to define the colony as morphologically transformed.
Statistics:
The linear correlation coefficient between the transformation frequency and Cr concentration was calculated and its statistical significance was testedat a confidence interval of 95%.

Results and discussion

Test results
Species / strain:
other: Syrian hamster embryo cells
Metabolic activation:
without
Genotoxicity:
positive
Cytotoxicity:
yes
Vehicle controls valid:
not examined
Negative controls valid:
not examined
Positive controls valid:
not examined
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Additional information on results:
A clear dose-response relationship for the induction of transformation was observed. At LD50 the transformation frequency was between 1.05-1.43%.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
positive

Zinc potassium chromate is cytotoxic and transforming.
Executive summary:

Twenty eight moderately water-soluble to insoluble chromium (VI) compounds, such as zinc, zinc potassium and lead chromate, industrial and laboratory synthesized pigments, and the analytical reagents strontium, barium and calcium chromate, were physicochemically characterized and studied for cytotoxicity and morphological transformation in cultured Syrian hamster embryo (SHE) cells. In vivo validation of malignancy of transformed SHE cells was performed. A high physicochemical diversity among the complex chromium pigments was revealed. The solubility of the compounds was greatly increased after incubation in a complete medium and even higher under cell culture conditions. The cytotoxic effects appeared to be due principally to extracellular solubilized chromium because the most solubilized compounds, Zn, Ca and Sr chromates, were equitoxic at about the same Cr concentration treatment and 8-fold more cytotoxic than less soluble compounds such as some Pb chromates and Ba chromate. However, certain physicochemical properties of lead chromate pigments could also influence their cytotoxic activity. All test compounds were, in a dose-dependent manner, efficient in inducing morphological transformation of SHE cells. Many of the Cr pigments, although physicochemically different, were similarly effective in transformation induction. Nevertheless, compounds among Zn and Pb chromates had various transforming potencies. Ba chromate was the least active in inducing transformation. Certain physicochemical properties could mediate the transforming activity but no particular relationship could be established between any one of the physicochemical parameters and the transforming potency. Cloned morphologically-transformed colonies of SHE cells were grown in soft agar medium and showed true neoplastic behaviour by tumour formation in syngeneic animals. These results show that various chromate pigments containing either Zn or Pb, of medium to very low aqueous solubility, induced neoplastic transformation of SHE cells.