Chromium trinitrate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

N/A

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well conducted, fulfill basic scientific requirements and was reported in well-known publication

Data source

Reference

Reference Type:

publication

Title:

Cyto toxic mutagenic and clastogenic effects of industrial chromiumcompounds.

Author:

Venier, A. Montaldi, F. Majone, V. Bianchi and A.G. Levis.

Year:

1982

Bibliographic source:

Carcinogenesis (1982) 3 (11): 1331-1338. P.

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

not specified

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

chromium nitrate

IUPAC Name:

chromium nitrate

Test material form:

not specified

Details on test material:

three Cr(III) references (chromium chloride, CrCI3, and two different preparations of chromium nitrate, Cr(NO3)3).
Chromium nitrate, from Merck and Riedel De Haen
chemical position: Cr(NO3)3.9H2O,

Method

Target gene:

histidine requiring S. typhimurium

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA 1535, TA 1538, TA 98 and TA 100

Details on mammalian cell type (if applicable):

N/A

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9 mix rat liver mkrosomal fraction induced by Aroclor

Test concentrations with justification for top dose:

0.027, 0.217, 6.968 and 13.937 mg/plate

Vehicle / solvent:

water/IN HC1

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Remarks:

withou s9

Positive control substance:

methylmethanesulfonate

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Remarks:

with s9

Positive control substance:

other: Aminofluorene

Details on test system and experimental conditions:

Rats were injected i.p. with Aroclor (Analabs, North Haven, CT) 500 mg/kg body weight.
Cell treatments were performed with Cr compounds freshly sdubflized in water or HCL. Concentrated solutions were filtered through a 0.22 µm Millipore membrane, and diluted 50 x with growth medium. In these condi-tions neither tccridty nor dastogenkity was caused by the diluted HCL.

Evaluation criteria:

N/A

Statistics:

N/A

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA 1535, TA 1538, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Contaminated Riedel chromium (III) nitrate was comparatively more cytotoxic.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

not specified

Additional information on results:

Riedel, but not Merck, chromium (III) nitrate, and chromite were also mutagenic in stains TA 100 at highest dose of 13.937 mg/plate, which was contaminated by Cr (VI) compounds. All other Cr(III) industrial com-pounds were inactive.
Reference Cr(III) (chromium chloride and Merck chromium nitrate) were only weakly cytotoxic even at 300 µg/ml Cr(III), which was the maximum solubility in complete growth medium. Riedel chromium (III) nitrate was comparatively more cytotoxic, the contamination with Cr(VI) accounting for such an effect.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with and without metabolic activation

Test substance was found negative of causing gene mutation in bacteria reverse mutation assay based on the results given in this report.

Executive summary:

The mutagenic effects of Cr compounds were determined with the S. typhimurium/microscme assay on strains TA1535, TA1538, TA98, and TA100. Water soluble and insoluble Cr compounds were tested in the plate incorporation assay, with or without the addition of the S9 mix rat liver microsomal fraction, according to the methods decribed by OECD guideline 471. Experiments were run in duplicate and were repeated at least twice for each compound. Reference Cr(III) (chromium chloride and Merck chromium nitrate) were only weakly cytotoxic even at 300 µg/ml Cr(III), which was the maximum solubility in complete growth medium. Riedel chromium (III) nitrate was comparatively more cytotoxic, the contamination with Cr(VI) accounting for such an effect. Riedel, but not Merck, chromium (III) nitrate, and chromite were also mutagenic in strains TA 100 at highest dose of 13.937 mg/plate, which was contaminated by Cr (VI) compounds. All other Cr(III) industrial compounds were inactive.

Therefore, under this conditions, chromium (III) nitrate resulted devoid of gene mutation in bacterial reverse mutation assay, but indicate that Cr (III) compounds can be contaminated by Cr(VI) and then may be found to be mutagenic.