Bis(2-methylisouronium) sulphate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian cell study: DNA damage and/or repair

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

prepared according to an old guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1989

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 486 (Unscheduled DNA Synthesis (UDS) Test with Mammalian Liver Cells in vivo)

Principles of method if other than guideline:

Test according to G. M. Williams "The detection of chemical mutagens-carcinogens by DNA repair and mutagenesis in liver cultures." 1980

GLP compliance:

yes

Type of assay:

unscheduled DNA synthesis

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2-methylisouronium) sulphate

EC Number:

257-851-8

EC Name:

Bis(2-methylisouronium) sulphate

Cas Number:

52328-05-9

Molecular formula:

C4H14N4O6S

IUPAC Name:

O-methyl-isourea sulphate

Test animals

Species:

rat

Strain:

Fischer 344

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

positive

Toxicity:

not examined

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Interpretation of results: positive
In three independent trials the test material O-Methylisourea sulphate induced significant increases in the nuclear labeling of rat primary hepatocytes. The test material O-Methylisourea sulfate was therefore evaluated as positive in the rat primary hepatocyte UDS Assay for an applied concentration range of 1000mg/L to 10.0 mg/L

Executive summary:

In the in vitro rat primariy hepatocyte unscheduled DNA synthesis (UDS) assay, the test material O-Methylisourea Sulfate, induced significant increases in UDS in hepatocyte obtained from each of four rats.

In the asseays described in this report, rat primary hepatocytes, derived from four different rats, were exposed to O-Methylisoruea Sulfate at concentrations ranging from 5000 µg/ml to 0.500 µg/ml. Treatments from 5000 µg/ml to 2000 µg/ml were lethal to hepatocytes in all trials. Treatments from 1000 µg/ml to 600 µg/ml were variably toxic with some trials showing cell morphologies suitable for analysis of UDS.

Treatments from 1000µg/ml to 10.0 µg/ml which covered a good range of toxicity (54.9% to 114.5% survival) werde analyzed for nuclear labeling in trial 1. In the next trial analysed a range of six treatments from 600 µg/ml to 25 µg/ml were analysed (70.2% to 99.3% survival) were chosen for analysis in the final trial. The test material was soluble in media at all concentrations tested.

Both of the criteria for a positive response were met with hepatocytes from three of the for rats tested. Hepatocytes from the fourth rat demonstrated significant increases in the percent of cells in UDS (net nuclear grains >=6) along with smaller elevations in the net nuclear grain count.

The test material, O-Methylisourea Sulfate, was therefore evaluated as active in the Rat Primariy Hepatocyte UDS Assay.