Manganese di(acetate)

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read-across substance, only 4 instead of 5 strains tested, but well performed and documented

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1986

Reference 2

Reference Type:

publication

Title:

Salmonella mutagenicity test results for 250 chemicals

Author:

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

Year:

1983

Bibliographic source:

Environ Mutagen S(Suppl. 1):3-142 (1983)

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 used; TA 102 was not yet developed

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Manganese (II) sulphate monohydrate

IUPAC Name:

Manganese (II) sulphate monohydrate

Constituent 2

Reference substance name:

10034-96-5

EC Number:

600-072-9

Cas Number:

10034-96-5

IUPAC Name:

10034-96-5

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): Manganese (II) sulfate monohydrate
- Molecular formula (if other than submission substance): MnSO4*H20
- Supplier: J.T. Baker
- test material was tested encoded in two independent laboratories
- Analytical purity: >99%:

Method

Target gene:

his-

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA 1535, TA 1537, TA 97, TA 98, TA 100

Details on mammalian cell type (if applicable):

- Type and identity of media: Oxoid Nutrient Broth #2 (CM67) (EGG) / minimal glucose medium (SRI)
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: no data
- Periodically checked for karyotype stability: no data
- Periodically "cleansed" against high spontaneous background: yes

Metabolic activation:

with and without

Metabolic activation system:

Arochlor 1254 induced S-9 fractions from male Sprague-Dawley rats and male Syrian hamsters

Test concentrations with justification for top dose:

at least five different concentrations, up to 10 mg/plate

Vehicle / solvent:

distilled water

Controls

Controls 1

Positive controls:

yes

Positive control substance:

other: 4-nitro-0-phenylenediamine

Remarks:

for strain TA98

Controls 2

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

for strains TA 1535 and TA 100

Controls 3

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

for strains TA 97 and TA 1537

Controls 4

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

for all strains, with hamster and rat liver metabolic activation systems

Controls 5

Untreated negative controls:

yes

Positive control substance:

other: potassium chloride

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 min
- Exposure duration: 48 h

SELECTION AGENT (mutation assays): histidine

NUMBER OF REPLICATIONS: three plates per dose level, tests were repeated completely

DETERMINATION OF CYTOTOXICITY
- Method: other: toxicity was evidenced by one or more of the following phenomena: appearance of his pinpoint colonies, reduced numbers of revertant colonies per plate, or thinning or absence of the bacterial lawn

Evaluation criteria:

1) mutagenic response: a dose-related, reproducible increase in the number of revertants over background, even if the increase was less than twofold;
2) nomutagenic response: when no increase in the number of revertants was elicited by the chemical;
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

Statistics:

no data

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 97, TA 98, TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

with and without metabolic activation

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not applicable

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

Study was well performed in two independent laboratories (test material encoded) similar to OECD guideline 471 with minor deviations. Therefore, the results can be considered to be reliable. Additionally, MnSO4 is considered to be suitable for read-across to manganese acetate. Hence, it can be concluded that Manganese acetate reveals negative results in the Ames test on Salmonella typhimurium with and without metabolic activation.

Executive summary:

In a reverse gene mutation test in bacteria (Ames test), strains TA 1535, TA 1537, TA 97, TA 98 and TA 100 of S. typhimurium were exposed to Manganese (II) sulphate monohydrate in distilled water in at least five different concentrations up to 10 mg/plate in the presence and absence of mammalian metabolic activation (hamster and rat S9, preincubation). The positive controls induced the appropriate responses in the corresponding strains.

There was no evidence of induced mutant colonies over background.

The study is classified as acceptable due to its good execution similar to OECD 471 with only minor restrictions and satisfies the requirements for Test Guideline OECD 471 for in vitro bacterial gene mutation data.