Bis(N,N',N''-trimethyl-1,4,7-triazacyclononane)-trioxo-dimanganese (IV) di(hexafluorophosphate)monohydrate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008

Reliability:

1 (reliable without restriction)

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)

Deviations:

not specified

Principles of method if other than guideline:

no data

GLP compliance:

not specified

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Bis(N,N',N''-trimethyl-1,4,7-triazacyclononane)-trioxo-dimanganese (IV) di(hexafluorophosphate)monohydrate

EC Number:

411-760-1

EC Name:

Bis(N,N',N''-trimethyl-1,4,7-triazacyclononane)-trioxo-dimanganese (IV) di(hexafluorophosphate)monohydrate

Cas Number:

116633-53-5

Molecular formula:

C18 H42 Mn2 N6 O3 . 2 F6 P

IUPAC Name:

dimanganese(4+) bis(1,4,7-trimethyl-1,4,7-triazonane) bis(hexafluoro-λ⁵-phosphanuide) hydrate trioxidandiide

Details on test material:

no data

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

no data

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

Aqueous 1% methylcellulose

Details on exposure:

A preliminary toxicity test had previously shown that 2000 mg/kg, which is the maximum recommended dose for this assay was tolerated.

Duration of treatment / exposure:

Sacrifice times: 24 and 40 hour

Frequency of treatment:

single acute oral administration

Post exposure period:

48 hours

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
500 mg/kg
Basis:
actual ingested

Doses / concentrations 2

Remarks:

Doses / Concentrations:
1000 mg/kg
Basis:
actual ingested

Doses / concentrations 3

Remarks:

Doses / Concentrations:
2000 mg/kg
Basis:
actual ingested

No. of animals per sex per dose:

5 males and 5 females

Control animals:

yes, concurrent vehicle

Positive control(s):

The positive control group was treated with mitomycin C at 12 mg/kg body weight

Examinations

Tissues and cell types examined:

Erythrocytes

Details of tissue and slide preparation:

no data

Evaluation criteria:

no data

Statistics:

no data

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

At the 48 hour sampling time mice treated with Commercial Dragon II did not show any significant increase in the frequency of micronucleated polychromatic erythrocytes. At the 24 hour sampling time a small but statistically significant increase in the incidence of micronuleated cells was obtained for the intermediate dose level of the test substance. However there was no evidence of a dose-response and all groups means as well as individual incidences of micronucleated cells for Commercial Dragon II at this sampling time fell well within the historical control range.
There was no substantial decrease in the ratio of polychromatic to normochromatic erythrocytes after treatment of the animals with Commercial Dragon II.
The positive control compound produced large, highly significant increases in the frequency of micronucleated polychromatic erythrocytes together with decrease in the ratio of polychromatic to normochromatic erythrocytes.

Any other information on results incl. tables

DOSES PRODUCING TOXICITY: Clinical signs consisting of pilo-erection were seen in both male and female animals, up to 3 hours after dosing.

OBSERVATIONS: At the 24 hour sampling time a small but statistically significant increase (P<0.001) in the incidence of micronucleated cells was obtained for the intermediate dose level of the substance. however there was no evidence of a dose response relationship and all group means and individual incidences of micronucleated cells at this time point fell within the historical control range. A re-examination of the slides from the 24 hour sampling time by a second slide reader failed to show any significant increase of micronucleated cells. The test substance did not cause any statistically significant increase in the number of micronucleated polychromatic erythocytes at the 48 hour sampling time.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Commercial Dragon II has not shown any evidence of causing chromosome damage in this in vivo test

Executive summary:

Results: Negative

Sacrifice times: After 24 and 40 hours

OBSERVATIONS: At the 24 hour sampling time a small but statistically

significant increase (P<0.001) in the incidence of

micronucleated cells was obtained for the intermediate dose

level of the test substance. However there was no evidence

of a dose-response relationship and all group means and individual

incidences of micronucleated cells at this time point fell

within the historical control range. A re-examination of

the slides from the 24 hour sampling time by a second slide

- reader failed to show any significant increase of

micronucleated cells.

The test substance did not cause any statistically

significant increase in the number of micronucleated

polychromatic erythocytes at the 48 hour sampling time.