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Toxicological information

Genetic toxicity: in vitro

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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

Constituent 1
Chemical structure
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.

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