Chromium trifluoride

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Peer reviewed publication
As with all metal salts, the significance for toxicity is the presence of specific ions that will form when in solution or when in biological systems.In the case of Cr III salts, the counter ion will have an effect on solubility and this is itself dependant on the type of media being used and in particular the pH of that media. It is generally accepted that in the case of metal salts, testing with salts that are soluble in the respective test media will ensure maximum exposure of the metal ions. This will include chlorides and nitrates as being more soluble and will indeed have relevance when dissolved in acid media, such as if ingested.
Read-across to other chromium III salts is therefore considered valid as long as the exposure in the test system is greater than would be expected for the substance under review for registration

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2005

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test using the Hprt and xprt genes)

Principles of method if other than guideline:

The study was conducted in two phases. The first phase evaluated the effect of Cr III in the CHO/Hprt gene mutation test for the standard exposure
period of 5 h with and without metabolic activation with an independent repeat assay.
The second phase evaluated the effect of Cr III in a CHO/Hprt gene mutation test with a 48 h exposure period in the absence of metabolic activation duplicate treatment conditions. The test conditions, sub-culturing and expression periods were the same following either the 5 or 48 h exposures to Cr III
and control agents.

GLP compliance:

not specified

Type of assay:

in vitro mammalian cell gene mutation test using the Hprt and xprt genes

Test material

Test material information

Constituent 1

Reference substance name:

Chromium chloride, basic

EC Number:

256-852-0

EC Name:

Chromium chloride, basic

Cas Number:

50925-66-1

Molecular formula:

Cr(Cl)x(OH)y where x + y = 3 (but x and y are > 0 and < 3

IUPAC Name:

chromium hydroxychloride

Constituent 2

Reference substance name:

chromium (III) picolinate

IUPAC Name:

chromium (III) picolinate

Details on test material:

Reagent grade chromium chloride was purchased from Fisher Scientific Co (Pittsburgh, PA) and picolinic acid was purchased from Sigma Chemical Co (St Louis, MO). Chromium picolinic acid was synthesised by heating 300 ml of deionised water to 80C and adding 150 mmol of picolinic acid. Fifty mmol of chromic chloride were then added in five equal portions; each fraction was dissolved before subsequent fractions were added. The solution was stirred at 80C for 30 minutes and turned from green to dark red. The pH was then adjusted with concentrated ammonium hudroxide to pH 6.0. Solution was then stirred for 30 minutes at 80C and cooled in an ice bath for 1 hour. Chromium picolinic acid crystals were filtered, washed with deionised water, washed with ethanol, and dried in a vacuum at 60C. Yield was 98.6% of theoretical expected results.

Specific details on test material used for the study:

Food grade - dietary supplement

Method

Target gene:

Hprt

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver S9
Prepared by the testing facility, BioReliance, Rockville, MD

Test concentrations with justification for top dose:

15.6, 31.3, 62.5, 125, 250, and 500µg/mL
Precipitate at 500 µg/ml

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

ethylmethanesulphonate

Details on test system and experimental conditions:

Repeat assays performed at 5 and 48 hour exposure periods
The 48 hour exposure period was without S-9 only

Results and discussion

Test results

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

Precipitate at top concentration tested

Any other information on results incl. tables

The results were consistent irresepctive of exposure period

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study, the Cr III salt tested up to precipitating dose levels in the culture medium was non-mutagenic in the standard CHO/Hprt assay + or −S9 activation