Copper dichromium tetraoxide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

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

Study period:

18/09/1990-21/02/1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline-compliant, GLP-compliant proprietary study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Chromoxid Extra

IUPAC Name:

Chromoxid Extra

Constituent 2

Reference substance name:

Chromium (III) hydroxide

EC Number:

215-158-8

EC Name:

Chromium (III) hydroxide

Cas Number:

1308-14-1

Molecular formula:

Cr(OH)3

IUPAC Name:

1308-14-1

Details on test material:

The test material 'Chromoxid extra' is described as a dark green powder of purity 99.6%

Method

Target gene:

Reversion to histidine independence in Salmonella typhimurium

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Metabolic activation system:

Male rat liver S9 fraction (Aroclor 1254-induced)

Test concentrations with justification for top dose:

0, 8, 40 200, 1000 and 5000 ug/plate; with and without S9

Vehicle / solvent:

Deionised water

Controls

Untreated negative controls:

no

Remarks:

not required

Negative solvent / vehicle controls:

yes

Remarks:

deionised water

True negative controls:

no

Remarks:

not required

Positive controls:

yes

Remarks:

sodium azide, nitrofurantoin, 4-NPDA, 2-aminoanthracene

Details on test system and experimental conditions:

Ames test (plate incorporation assay). Triplicate plates of each strain were exposed to the test material (in deionised water) for 48 hours.

Evaluation criteria:

Negative controls within the expected range;
Positive controls showing sufficient effects;
Reproducible and dose-related increase in mutant counts of at least one strain (2x for TA1535, TA100, TA98; 3x for TA1537)

Statistics:

Not applicable

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Remarks:

Precipitation was seen at 1000 and 5000 ug/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

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

Exposure to the test material did not induce any increase in the number of revertant colonies of any bacterial strain. Positive control compounds induced large increased in the number of revertant colonies, confirming the sensitivity of the assay.

Treatment	-S9
	Initial assay				Confirmatory assay
	TA98	TA100	TA1535	TA1537	TA98	TA100	TA1535	TA1537
Vehicle	20	114	12	9	34	130	15	11
8	16	125	13	9	36	123	18	9
40	26	127	15	9	34	141	20	13
200	21	133	16	7	29	138	21	12
1000	22	109	11	7	34	132	17	13
5000	20	127	12	9	34	146	21	14
Nitrofurantoin		382				416
4-NPDA	86			56	105			58
Sodium azide			631				793
	+S9
	Initial assay				Confirmatory assay
	TA98	TA100	TA1535	TA1537	TA98	TA100	TA1535	TA1537
Vehicle	31	134	14	9	48	162	27	16
8	29	127	14	9	51	173	25	14
40	30	105	18	8	43	164	27	15
200	25	124	16	6	37	163	26	12
1000	25	125	16	9	35	174	23	14
5000	30	121	13	8	41	176	22	20
2-AA	427	817	99	134	570	1297	242	68

Applicant's summary and conclusion

Conclusions:

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

No evidence of mutagenicity was seen under the conditions of this assay.

Executive summary:

The mutagenicity of chromium hydroxide was investigated in an Ames test (plate incorporation assay) using S. typhimurium strains TA98, TA100, TA1535 and TA1537. Four replicate plates of each strain were exposed to the test material (suspended in deionised water) at concentrations of 0, 8, 40, 200, 1000 or 5000 ug/plate in the presence and absence of an exogenous metabolic activation system (Aroclor 1254 -induced male rat liver S9 fraction). There was no evidence of cytotoxicity at the limit concentration; precipitation of the test material was seen at 1000 and 5000 ug/plate. Exposure to the test material did not induce increased numbers of revertant colonies of any strain. Appropriate positive control compounds induced large increases in the numbers of revertant colonies, confirming the sensitivity of the assay. Results were confirmed in an independently-repeated assay. No evidence of mutagenicity was seen under the conditions of this study. The results of this study, performed using chromium (III) hydroxide, can be extrapolated to the similarly water-insoluble chromium (III) oxide salt.