Zirconium dichloride oxide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Well documented, scientifically sound study that is similar to OECD Guideline 471 "Bacterial Reverse Mutation Test", however, only four strains were evaluated and there was no strain present to detect cross linking mutagens. Study was run on 270 coded chemical samples multiple laboratories.

Data source

Reference

Reference Type:

publication

Title:

Salmonella Mutagenicity Tests: II. Results from the Testing of 270 Chemicals

Author:

Mortelmans K, Haworth S, Lawlor T, Speck W, Tainer B, Zeiger E

Year:

1986

Bibliographic source:

Environmental Mutagenesis 8(7): 1-119

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

only four strains were evaluated and there was no strain used to detect cross linking mutagens.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Zirconium dichloride oxide

EC Number:

231-717-9

EC Name:

Zirconium dichloride oxide

Cas Number:

7699-43-6

Molecular formula:

Cl2OZr

IUPAC Name:

Dichloro(oxo)zirconium

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): zirconium oxychloride
- Physical state: crystals

Method

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA1535, TA1537, TA98, and TA100

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced rat and hamster metabolic activation system

Test concentrations with justification for top dose:

10, 33, 100, 333, 1000, 3333, 6666 µg/L

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: ethanol (ET 95%)

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

no

True negative controls:

yes

Remarks:

Potassium chloride

Positive controls:

yes

Positive control substance:

other: Sodium azide (TA1535 and TA100); 4-nitro-o-phenylenediamine (TA98); 9-aminoacridine (TA1537); 2-aminoanthracene (all strains with hamster and rats liver metabolic activation systems). 9-aminoacridine hydrochloride H2O; 4-nitro-o-phenylenediamine

Details on test system and experimental conditions:

METHOD OF APPLICATION: The test substance was assayed for mutagenicity in a preincubation assay. The following was added to each test tube: 0.5 mL of S-9 mix or 0.1 M PO4 buffer (pH7.4), 0.05 mL of the overnight culture, and 0.05 mL of solvent. The mixture was mixed and allowed to incubate without shaking at 37 degrees C for 20 min, at which time 2.0 mL of molten top agar supplemented with 0.5 mM L-histidine and 0.5 mM D-biotin were added. The contents of the tubes were mixed and poured onto 25 mL of minimal glucose bottom agar in 15 x 100 mm plastic petri dishes. When the top agar had solidified, the plates were inverted and incubated at 37 degrees C for 48 hr.

DURATION
- Preincubation period: 20 mins
- Exposure duration: 48 hours
- Expression time (cells in growth medium): 48 hours
- Fixation time (start of exposure up to fixation or harvest of cells): 48 hours

SELECTION AGENT (mutation assays): L-histidine and D-biotin

NUMBER OF REPLICATIONS: 3

NUMBER OF CELLS EVALUATED: no data

Evaluation criteria:

The criteria used for data evaluation are summarized as follows: (1) mutagenic response: a dose-related, reproducible increase in the number of revertants over background, even if the increase was less than twofold; (2) nonmutagenic response: when no increase in the number of revertants was elicited by the test substance; (3) questionable response: when there was an absence of a clear-cut dose-related increase in revertants; when the dose-related increases in the number of revertants were not reproducible; or when the response was of insufficient magnitude to support a determination of mutagenicity.

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA1535, TA1537, TA98, and TA100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

not examined

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES: A preliminary dose-setting test was initiated with strain TA100, in the presence and the absence of the metabolica activation systems, over a wide dose range with an upper limit of 10 mg/plate, or less when solubility problems were encountered. Toxicity was acknowledged by one or more of the following parameters: appearance of his- pinpoint colonies, reduced number of revertant colonies per plate or thinning or absence of the bacterial lawn.

Remarks on result:

other: all strains/cell types tested

Applicant's summary and conclusion

Conclusions:

Under the test conditions and based on the results the test substance is non-mutagenic in the absence and presence of metabolic activation.