Ammonium molybdate(VI)

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro mammalian chromosome aberration test was performed to evaluate the mutagenic nature of ammonium molybdate. The study was performed at dose level of 10µM using human lymphocytes. The duration of exposure was 24 hrs. Ammonium molybdate induced chromosome aberrations in human lymphocytes and hence is likely to be mutagenic in vitro.

Link to relevant study records

Reference

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from Secondary literature

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

In vitro mammalian chromosome aberration test was performed to evaluate the mutagenic nature of ammonium molybdate

GLP compliance:

not specified

Type of assay:

other: Chromosomal aberration assay

Specific details on test material used for the study:

- Name of test material: Ammonium molybdate
- Molecular formula: MoO42H4N
- Molecular weight: 196.0132 g/mol
- Substance type: Inorganic
- Physical state: No data
- Purity: No data
- Impurities (identity and concentrations): No data

Target gene:

No data

Species / strain / cell type:

lymphocytes: Human

Details on mammalian cell type (if applicable):

No data

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

No data

Metabolic activation:

not specified

Metabolic activation system:

No data

Test concentrations with justification for top dose:

10 µM

Vehicle / solvent:

No data

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Details on test system and experimental conditions:

METHOD OF APPLICATION: No data

DURATION
- Preincubation period: No data
- Exposure duration: 24 hrs
- Expression time (cells in growth medium): No data
- Selection time (if incubation with a selection agent): No data
- Fixation time (start of exposure up to fixation or harvest of cells): No data

SELECTION AGENT (mutation assays): No data
SPINDLE INHIBITOR (cytogenetic assays): No data
STAIN (for cytogenetic assays): No data

NUMBER OF REPLICATIONS: No data

NUMBER OF CELLS EVALUATED: No data

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data

OTHER EXAMINATIONS:
- Determination of polyploidy: No data
- Determination of endoreplication: No data
- Other: No data

OTHER: No data

Rationale for test conditions:

No data

Evaluation criteria:

The slides were observed for induction of chromosome aberrations

Statistics:

No data

Species / strain:

lymphocytes: Human

Metabolic activation:

not specified

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

No data

Conclusions:

Ammonium molybdate induced chromosome aberrations in human lymphocytes and hence is likely to be mutagenic in vitro.

Executive summary:

In vitro mammalian chromosome aberration test was performed to evaluate the mutagenic nature of ammonium molybdate. The study was performed at dose level of 10µM using human lymphocytes. The duration of exposure was 24 hrs. Ammonium molybdate induced chromosome aberrations in human lymphocytes and hence is likely to be mutagenic in vitro.

Endpoint conclusion

Endpoint conclusion:

no study available (further information necessary)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Gene mutation in vitro:

Data from the target chemical and read across chemicals was reviewed to determine the mutagenic nature of Ammonium molybdate. The summary is as mentioned below:

In vitro mammalian chromosome aberration test was performed ( Dutch Expert Committee on Occupational Safety, a Committee of the Health Council of the Netherlands, 2013) to evaluate the mutagenic nature of ammonium molybdate. The study was performed at dose level of 10µM using human lymphocytes. The duration of exposure was 24 hrs. Ammonium molybdate induced chromosome aberrations in human lymphocytes and hence is likely to be mutagenic in vitro.

In the same study, Micronucleus assay was performed to evaluate the mutagenic nature of ammonium molybdate. The study was performed at dose level of 0.1- 2 mM using human lymphocytes. Ammonium molybdate induced a concentration-related increase of the number of micronucleated cells in human lymphocytes and hence is likely to be mutagenic in vitro. Viability of the cells ranged between 61% and 68%, which is above the minimum of 40 to 50% cell viability according to the OECD guidelines.

Sister chromatid exchange assay was performed to evaluate the mutagenic nature of ammonium molybdate. The study was performed at dose level of 10µM using human lymphocytes. The duration of exposure was 24 hrs. Ammonium molybdate induced sister chromatid exchange in human lymphocytes and hence is likely to be mutagenic in vitro.

Genetic toxicity test was performed on Saccharomyces cerevisiae / diploid D7 strains to study the effect of ammonium molybdate by gene conversion at the trp locus and reverse mutation at the ilv locus. A tube of YEPD broth (1% yeast extract, 2% peptone, 2% dextrose w/v) was inoculated with D7 and grown overnight at 30°C with shaking. Appropriate dilutions of 10⁶and 10⁵cells were spread on complete growth medium. After the spread aliquot had 'dried, a centre well was made by pressing the mouth of a sterile (8 cm × 1 cm) test tube into the medium and the agar plug was removed with sterile forceps. Salts were dissolved in sterile distilled water at a concentration of 0.1 M and added to the well. Plates were incubated overnight at 30°C. As the solution diffuses into the medium a concentration gradient is produced, and a zone of killing around the well indicates chemical toxicity. These plates were replica plated onto medium lacking tryptophan and medium lacking isoleucine and valine. The plates were observed for gene conversion at trp and reverse mutation at ilv were indicated by a ring of colonies on the tryptophanless and isoleucineless plates. Ammonium molybdate did not induce gene conversion at trp and reverse mutation at the ilv locus in the yeast Saccharomyces cerevisiae and hence it is not likely to classify as a gene mutant in vitro.

In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by Zeiger et al (Environmental and molecular mutagenesis, 1992) to determine the mutagenic nature of molybdenum trioxide (RA CAS no 1313 -27 -5). The study was performed using Salmonella typhimurium strains TA97, TA98, TA100, TA1535 and TA1537 in the presence and absence of S9 metabolic activation system. The chemical was dissolved in acetone as solvent and used at dose levels 0, 10, 33, 100, 333, 1000, 3333 or 10000 µg/plate by the preincubation method. The doses were selected on the basis of preliminary dose range finding study and concurrent solvent and positive controls were included in the study. Molybdenum trioxide did not induce mutation in Salmonella typhimurium TA97, TA98, TA100, TA1535 and TA1537 in the presence and absence of S9 metabolic activation system and hence is not likely to classify as a gene mutant in vitro.

The studies summarized to determine the mutagenic nature of ammonium molybdate are inadequate to conclude whether or not the test chemical showed clastogenic effect. Also in the another study mentioned, the increase in the micronucleated cells was minimal. Thus, based on the other data available for the target chemical and its read across, Ammonium molybdate does not exhibit gene mutatation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro. Further testing must be supported to determine the mutagenic nature of ammonium molybdate.

Justification for classification or non-classification

The studies summarized to determine the mutagenic nature of ammonium molybdate are inadequate to conclude whether or not the test chemical showed clastogenic effect. Also in the another study mentioned, the increase in the micronucleated cells was minimal. Thus, based on the other data available for the target chemical and its read across, Ammonium molybdate does not exhibit gene mutatation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro. Further testing must be supported to determine the mutagenic nature of ammonium molybdate.