Indium trihydroxide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

Indium trihydroxide

EC Number:

243-947-7

EC Name:

Indium trihydroxide

Cas Number:

20661-21-6

Molecular formula:

H3InO3

IUPAC Name:

indium trihydroxide

Test material form:

solid: particulate/powder

Details on test material:

Name: Indium trihydroxide
Synonym: Indium(III) hydroxide
Batch/Lot number: OH-1306
Molecular formula: In(OH)3
Molecular weight: 165.84
Appearance: White powder
Purity: 72.9% indium
Expiry date: 02 November 2013
Storage conditions: Room temperature (15-30oC)
Safety Precautions: Routine safety precautions (lab coat, gloves, safety glasses and face mask) for unknown materials were applied to assure personnel health and safety.

Method

Species / strain

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Metabolic activation system:

S9

Test concentrations with justification for top dose:

5000, 2500, 1250, 625 µg/mL

Vehicle / solvent:

distilled water

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Remarks:

EMS and CP

Positive control substance:

cyclophosphamide

ethylmethanesulphonate

Details on test system and experimental conditions:

Chromosome aberrations:

METHOD OF APPLICATION: in suspension

DURATION
- Preincubation period: 3 days
- Exposure duration: 20h (assay 1) and 28h (assay2)

SPINDLE INHIBITOR (cytogenetic assays): colchicine
STAIN (for cytogenetic assays): 5% Giemsa solution

NUMBER OF REPLICATIONS: two (per concentration and per assay)

NUMBER OF CELLS EVALUATED: at least 200 well-spread metaphase cells for each concentration (per assay). The examination of slides from a culture was halted when 15 or more metaphases with aberrations (excluding gaps) have been recorded for that culture

Evaluation criteria:

The test item is considered to have shown clastogenic activity in this study if all of the following criteria are met:
-Increases in the frequency of metaphases with aberrant chromosomes are observed at one or more test concentrations (only data without gaps will be considered).
-The increases are reproducible between replicate cultures and between tests (when treatment conditions were the same).
-The increases are statistically significant.
-The increases are not associated with large changes in pH or osmolarity of the treated cultures.

The historical control data for this laboratory were also considered in the evaluation. Evidence of a dose-response relationship (if any) was considered to support the conclusion.

The test item is concluded to have given a negative response if no reproducible, statistically significant increases are observed.

Statistics:

Fisher’s exact test

Results and discussion

Test results

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: +S9: no, but tested up to precipitating conc; -S9: yes

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Remarks:

valid historical negative controls database

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Chinese hamster V79 cells treated with indium trihydroxide up to 5000 µg/mL did not show any consistent genotoxic activity under the conditions of this study

Executive summary:

The test item Indium trihydroxide was tested for potential clastogenic activity using the Chromosome Aberration Assay. The study included two Concentration Selection Cytotoxicity Assays and two Chromosome Aberration Assays.

 

The performed experiments were considered to be valid and to reflect the real potential of the test item to cause structural chromosomal aberrations in the cultured V79 Chinese hamster cells used in this study.

 

The effect of the test item on the frequency of the cells with structural chromosome aberrations without gaps was investigated either in the presence or absence of a metabolic activation system which was a cofactor-supplemented post-mitochondrial S9 fraction prepared from the livers of phenobarbital/b-naphthoflavone induced rats. Although, statistically significantincrease was seen in the number of cells with structural chromosome aberrations in one case in the experiment with metabolic activation of Assay 1, it was not repeatable, and there was no evidence of any dose response.

 

Although there was an isolated positive response in only one of two replicates with metabolic activation (3h treatment, 20h harvest), the increase was not repeatable and there was no dose response. Hence it is concluded that this individual increase does not represent a positive effect of the test item.

In conclusion, Chinese hamster V79 cells treated with indium trihydroxide up to 5000 µg/mL did not show any consistent genotoxic activity under the conditions of this study.