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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Mutagenicity of chromium picolinate and its components in Salmonella typhimurium and L5178Y mouse lymphoma cells.
Author:
Whittaker, P. et al.
Year:
2005
Bibliographic source:
Food and Chemical Toxicology 43, 1619-1625

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
GLP compliance:
not specified
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): chromium picolinate, ESDA
- Molecular formula (if other than submission substance): C18H12CrN3O6
- Analytical purity: 99%

Method

Target gene:
thymidine kinase
Species / strain
Species / strain / cell type:
mouse lymphoma L5178Y cells
Details on mammalian cell type (if applicable):
- Type and identity of media: Fischer's medium for leukemic cells of mice supplemented with 10% horse serum and 0.02% pluronic F-68
- Periodically checked for Mycoplasma contamination: yes
Additional strain / cell type characteristics:
other: 3.7.C
Metabolic activation:
with and without
Metabolic activation system:
S9 from Aroclor 1254-induced male Sprague-Dawley rats
Test concentrations with justification for top dose:
50, 150, 500 and 1000 µg/mL
Vehicle / solvent:
distilled water
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
distilled water
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: without S9: methyl methanesulfonate; with S9: 7,12-dimethylbenzanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in suspension


DURATION
- Exposure duration: 4 h
- Expression time (cells in growth medium): 48 h
- Selection time (if incubation with a selection agent): 10 - 12 days
- Fixation time (start of exposure up to fixation or harvest of cells): 12 - 14 days


SELECTION AGENT (mutation assays): trifluorothymidine (TFT, 3 µg/mL)


NUMBER OF REPLICATIONS: duplicate cultures, three plates


DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency


OTHER EXAMINATIONS:
- Other: Determination of colony size
Evaluation criteria:
Indication of a mutagenic activity if there was evidence of a dose response with at least one concentration giving an increase in mutant frequency of at least 100 mutants per 1E+6 surviving cells above the concurrent control value.

Results and discussion

Test results
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Dose [µg/mL]

Rat S9

Relative total growth

[% of control]

Mutant frequency/106 survivors

Solvent control

0

-

100.0

85

50

-

98.5

122

150

-

84.5

87

500

-

76.0

380

1000

-

58.5

400

Positive control

(MMS)

10

-

43.0

401

Solvent control

0

+

100.0

60

50

+

114.5

61

150

+

94.5

94

500

+

86.5

237

1000

+

31.5

387

Positive control

(DMBA)

4

+

33.0

392

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
positive