Bismuth vanadium tetraoxide

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Two Ames tests (similar to OECD guideline 471), an in vitro mammalian chromosome aberration test (similar to OECD guideline 473), an in vitro mammalian HPRT test (similar to OECD guideline 476) and an in vivo micronucleus test with intraperitoneal exposure (according to OECD guideline 474) are available. All tests were negative.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Two Ames tests (similar to OECD guideline 471), an in vitro mammalian chromosome aberration test (similar to OECD guideline 473), an in vitro mammalian HPRT test (similar to OECD guideline 476) and an in vivo micronucleus test with intraperitoneal exposure (according to OECD guideline 474) are available. All tests were negative.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Ames

The test substance was tested for mutagenicity in the Ames test (standard plate test).

Strains: TA 1535, TA 100, TA 1537, TA 1538, TA 98

Dose range: 20 µg - 5000 µg/plate

Test conditions: Standard plate test with and without metabolic activation (S9 mix).

Solubility: Incomplete solubility of the test substance from 500 µg onward.

Toxicity: No bacteriotoxic effect (reduced his- background growth) was observed.

Mutagenicity: An increase in the number of his+ revertants could not be observed either without S9 mix or after addition of a metabolizing system.

Assessment: According to the results of the present study, the substance is thus not mutagenic in the Ames test under the experimental conditions chosen here. (BASF, 1983)

This test result is supported by the Ciba Ames test which comprised in addition to the S. typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 also E. coli WP2 uvrA.

Chromosome Aberration Assay

An in vitro mammalian chromosome aberration test was conducted in Chinese hamster lung fibroblasts (V79 cells) with and without metabolic activation (S9 mix from treated SD rats). 0.5 % carboxymethyl cellulose (CMC) were used as solvent. Positive controls were MMC and CPA. Application of the test substance was in medium for an exposure duration of 24 and 48 hours without metabolic activation and 6 hours with metabolic activation. 100 - 200 cells were evaluated. Mitotic index and relative total growth were determined to evaluate cytotoxicity. No genotoxicity was observed with and without metabolic activation at concentrations up to 5000 µg/mL. Therefore, the test substance is considered to be non-mutagenic in the chromosome aberration assay under the test conditions chosen.

HPRT

The study was performed to investigate the potential of the test substance to induce gene mutations at the HPRT locus in V79 cells of the Chinese hamster. The assay was performed in two independent experiments, using two parallel cultures each. The main experiments were performed with and without liver microsomal activation and a treatment period of 4 hours. The highest concentration (3240 µg/mL) of the pre-experiment and both main experiments was equal to a molar concentration of approximately 10 mM. The test item was suspended in deionised water. Precipitation of the test item was observed in experiment 1 at 1620 µg/mL and above with and without metabolic activation. In experiment 2 precipitation was noted at 500.0 µg/mL and above with and without metabolic activation. No relevant cytotoxic effect indicated by a relative cloning efficiency or cell density below 50 % in both parallel cultures was observed up to the highest concentration of both experiments with and without metabolic activation. No substantial and reproducible dose dependent increase of the mutation frequency was observed up to the maximum concentration with and without metabolic activation. Appropriate reference mutagens (EMS and DMBA), used as positive controls, induced a distinct increase in mutant colonies and thus, showed the sensitivity of the test system and the activity of the metabolic activation system. In conclusion it can be stated that under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells. Therefore, the test substance is considered to be non-mutagenic in this HPRT assay.

Micronucleus Test in vivo

The in vivo micronucleus test was conducted with intraperitoneal administration because the acute tests with the test material bismut vanadate had pointed to a lower oral bioavailability of the test compound compared to soluble vanadates. Soluble vanadates proved positive in the micronucleus assay following oral administration, however, the soluble vanadium pentoxide was negative following inhalation exposure. To maximize the exposure to the poorly soluble bismut vanadate, intraperitoneal administration was chosen which could have revealed a micronucleus induction by even small amounts of solubilized test material which would most likely have been missed by oral and would surely have been missed by inhalation exposure. The test substance did not lead to an increase in the number of polychromatic erythrocytes containing either small or large micronuclei up to doses of 2000 mg/kg bw. The PCE/NCE ratio was uneffected, i.e. no inhibition of erythropoiesis was induced by the test substance.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. No adverse findings or genotoxicity was observed in in vitro or in vivo studies. As a result, the substance is not considered to be classified for mutagenicity under Regulation (EC) No. 1272/2008.