Bis(5-oxo-L-prolinato-N1,O2)copper

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

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:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Bis(5-oxo-L-prolinato-N1,O2)copper

EC Number:

239-471-4

EC Name:

Bis(5-oxo-L-prolinato-N1,O2)copper

Cas Number:

15454-74-7

Molecular formula:

C10H12CuN2O6

IUPAC Name:

bis(5-oxo-L-prolinato-N1,O2)copper

Method

Target gene:

Histidine operon

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Metabolic activation system:

The system used is a cofactor enhanced post-mitochondrial fraction (S9), prepared from rat livers treated with an enzymatic inducer.

Test concentrations with justification for top dose:

According to OECD Guideline, 5 concentrations of test item have been studied with approximately half log (i.e. approximately v10) interval. These doses (rounded to the higher value) used for the preliminary cytotoxicity test were therefore the following: 5000, 1600, 500, 160 and 50 µg/plate.
As the preliminary experiment revealed no cytotoxicity of the test item, this range of concentrations has been conserved for the Test 1.

Vehicle / solvent:

Test item: deionized water

Positive controls:
2-nitrofluorene: DMSO
Sodium azide: water
Mitomycin: water
9-aminocridine: DMSO
2-aminoanthracene: DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

other: Mitomycin, 2-aminoanthracene

Details on test system and experimental conditions:

Test 1 (direct method) : Incubate at 37°C ± 2°C for 48 to 72 hours.
Test 2 (method with pre-incubation) :
Incubate at 37°C ± 2°C for 20 to 30 min.
- Add the 2 ml of top agar.
- Mix and pour on the surface of the bottom agar previously distributed in Petri dishes.
- Incubate at 37°C ± 2°C for 48 to 72 hours.

Evaluation criteria:

The test is considered valid if the following criteria are fulfilled:
- The sterility tests are conform,
- The mean negative controls are within the historical data,
- The solvent used (negative control) must not show genotoxic nor cytotoxic activity,
- The revertants rate obtained for the positive controls must be in agreement with the historical data,
- The positive controls must show a revertants number equal at least to the double of the spontaneous rate of reversion for TA98, TA100 and TA102 (R ¿ 2) and the triple of the spontaneous rate of reversion for TA1535 and TA1537 (R ¿ 3),
- No more than 5% of the plates of the test are lost through contamination or any other unforeseen event,
- At least 3 concentrations are available for mutagenicity assessment.

Results and discussion

Test results

Key result

Species / strain:

other: All strains

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Based on OECD 471, GLP study, COPPER PCA - REF : C0018 was found to be non mutagenic and non pro-mutagenic under the test conditions.