Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

Administrative data

Endpoint:
in vitro DNA damage and/or repair study
Remarks:
Type of genotoxicity: DNA damage and/or repair
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: scientifically acceptable publication

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Cytotoxic and clastongenic effects of soluble and insoluble compounds containing hexavalent and trivalent chromium.
Author:
Levis AG and Majone F
Year:
1981
Bibliographic source:
Br J Cancer 44: 219-235
Reference Type:
secondary source
Title:
No information
Author:
IARC Monographs
Year:
1990
Bibliographic source:
Chromium and Chromium compounds. Vol. 49, WHO, Geneva (Switzerland)

Materials and methods

Principles of method if other than guideline:
Method: Levis AG et al. (1979), Br J Cancer 40: 523
GLP compliance:
no
Type of assay:
other: in vitro mammalian chromosome aberration test and sister chromatid exchange assay in mammalian cells

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): chromium Yellow (industrial pigment kindly supplied by Dr Cesare Maltoni (Istituto di Oncologia "Felice Addarii", Bologna, Italy)
- Analytical purity: not specified
- Impurities (identity and concentrations): see bellow
- Composition of test material, percentage of components: PbCrO4 (41-85%); PbSO4 (4-45%); Si02 (0.1-3%); Al2O3 (2-6%)

Method

Species / strain
Species / strain / cell type:
other: CHO-Zellen
Details on mammalian cell type (if applicable):
- Type and identity of media: Eagle's minimal essential medium (MEM) supplemented with 10% calf serum
- Properly maintained: yes
Metabolic activation:
without
Test concentrations with justification for top dose:
0, 5, 25, 150 µg/mL
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: test subtance was directly given to the culture medium
Controls
Untreated negative controls:
yes
Remarks:
cell culture medium
Negative solvent / vehicle controls:
yes
True negative controls:
other: additional compounds were also tested showing negative results (Table 1)
Positive controls:
other: additional compounds were also tested showing positive results (Table 1)
Positive control substance:
other: see above
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 32 hours in MEM (2 division cycles)
- Expression time (cells in growth medium): 8 x 10E-5 M bromodeoxyuridine Sigma, St Louis, Mo., U.S.A.) was incorporated for 2 cell cycles (32 h) in CHO cell cultures, and then metaphase cells were prepared so that chromosome aberrations and sister-chromatid exchanges (SCE) were scored on the same cell preparations.

DETERMINATION OF CYTOTOXICITY
- Method:relative total growth; cell growth was estimated on the basis of the DNa+RNA content of treated cultures.

- no additional data

Results and discussion

Test results
Metabolic activation:
without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
other: cell growth was 48% of control at concentration level of 150 µg/ml
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
other: additional compounds were also tested showing positive results (Table 1)
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: Chromosome aberrations and sister chromatid exchanges induced by Cr(VI) and Cr(III) compounds in CHO cell cultures

Treatment

Concentrations (µg/ml)

Cell growth (% of control)

Metaphases counted

Chromosome and chromatid aberrations per 100 metaphases

SCE/metaphase

t-values for SCE/metaphase (for comparison with control)  

p-values smaller than

-

-

100

61

13.3

7.47±0.11

-

-

Chomium yellow (VI)

5

89

95

29.2

9.34±0.19

7.42

.0.001

25

78

40

22.5

9.90±0.29

9.11

.0.001

150

48

-

-

-

-

-

Chromium orange (VI)

5

100

75

25.0

9.36±0.25

6.50

.0.001

25

93

30

26.7

10.47±0.29

11.66

.0.001

150

56

-

-

-

-

-

Molybdenum orange (VI)

5

100

75

20.0

10.48±0.38

8.33

.0.001

25

100

30

24.4

10.11±0.36

8.01

.0.001

150

85

-

26.0

9.76±0.13

12.28

.0.001

Zinc yellow (VI)

5

73

75

28.6

13.14±1.10

10.11

.0.001

25

29

30

-

-

-

-

150

10

-

-

-

-

-

Potassium dichromate (VI)

0.3

83

64

32.5

12.84±0.51

10.08

.0.001

Neochromium (III)

5

100

30

20.0

7.46±0.22

0.05

.>0.7

25

100

30

23.3

7.57±0.18

0.50

.>0.5

150

100

30

26.7

7.62±0.22

0.69

.>0.4

Chromium alum (III)

5

100

40

15.0

7.21±0.18

1.25

>0.NR

25

100

40

20.0

7.40±0.20

0.34

.>0.NR

150

100

28

28.6

7.53±0.31

0.23

.>0.7

Chromite (III)

5

100

65

26.5

9.49±0.31

6.02

.0.001

25

100

62

23.4

8.27±0.30

2.52

.0.02

150

88

-

-

-

-

-

Chromium sulfate (III)

5

100

40

10.0

7.10±0.17

1.80

.>0.05

25

100

40

22.5

7.45±0.27

0.79

.>0.4

150

93

60

25.0

7.73±0.35

0.72

.>0.4

Chromium chloride (III)

50

95

34

29.4

7.20±0.41

0.81

.>0.4

Applicant's summary and conclusion