Bis(pentane-2,4-dionato-O,O')zinc

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / micronucleus study

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

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 487 (In vitro Mammalian Cell Micronucleus Test)

GLP compliance:

yes (incl. QA statement)

Type of assay:

in vitro mammalian cell micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

Bis(pentane-2,4-dionato-O,O')zinc

EC Number:

237-860-3

EC Name:

Bis(pentane-2,4-dionato-O,O')zinc

Cas Number:

14024-63-6

Molecular formula:

C10H14O4Zn

IUPAC Name:

zinc bis(4-oxopent-2-en-2-olate)

Test material form:

solid: particulate/powder

Method

Species / strain

Species / strain / cell type:

human lymphoblastoid cells (TK6)

Details on mammalian cell type (if applicable):

For each experiment, sufficient whole blood was drawn from the peripheral circulation of a volunteer who had been previously screened for suitability.

Metabolic activation:

with and without

Test concentrations with justification for top dose:

The dose levels used in the main experiments were selected using data from the preliminary toxicity test and were as follows:
- 4-hour without S9: 10,20,40, 50,60, 80 µg/mL
- 4-hour with S9 (2%): 20,40, 80, 100, 120, 160 µg/mL
- 20-hour without S9: 10,20,40,50,60,80 µg/mL
- 4-hour with S9 (1 %): 20,40,80, 100, 120, 160 µg/mL

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

no

True negative controls:

no

Positive controls:

yes

Positive control substance:

cyclophosphamide

mitomycin C

other: demecolcine

Details on test system and experimental conditions:

Duplicate cultures of human lymphocytes, treated with the test item, were evaluated for micronuclei in binucleate cells at up to four dose levels, together with vehicle and positive controls. Four exposure conditions were used for the study. Experiment 1 used a 4 hour exposure in the presence and absence of a standard metabolising system (S9, at a 2% final concentration). Experiment 2, used a repetition of the 4 hour exposure with S9 (at a 1 % final concentration), whilst in the absence of metabolic activation the exposure time was increased to 20 hours.

Statistics:

The frequency of cells with micronuclei was compared, where necessary, with the concurrent vehicle control value using the Chi-squared Test on observed numbers of cells with micronuclei.

Results and discussion

Test results

Key result

Species / strain:

human lymphoblastoid cells (TK6)

Metabolic activation:

with and without

Genotoxicity:

ambiguous

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

The test item induced weak but statistically significant increases in the frequency of cells with micronuclei in both the absence and presence of a metabolising system at dose levels which achieved less than optimum toxicity. Due to the relatively weak responses the test item cannot conclusively be considered to be clastogenic and aneugenic to human lymphocytes in vitro but conversely the indications of a response at dose levels which achieved less than optimum toxicity cannot be ignored and therefore an equivocal result has to be given.