Bis(2-methylisouronium) sulphate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

'O-Methylisoharnstoffsulfate (technisch)' was examined for mutagenic activity in the Ames test using the histidine requiring S. typhimurium mutants TA 1535, TA 1537, TA 98 and TA 100 as indicator strains and a liver microsome fraction of Aroclor-induced rats for metabolic activation.

It was concluded that 'O-Methylisoharnstoffsulfat (technisch)' did not show any mutagenic activity in the Ames test.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

only 4 sstrains tested

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

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

Metabolic activation:

with and without

Test concentrations with justification for top dose:

concentrations of 0.62; 1.85; 5.56;16.67 and 50mg/l in water were used

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

True negative controls validity:

not specified

Positive controls validity:

not specified

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

True negative controls validity:

not specified

Positive controls validity:

not specified

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

True negative controls validity:

not specified

Positive controls validity:

not specified

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

True negative controls validity:

not specified

Positive controls validity:

not specified

Conclusions:

From the findings of the test it is concluded that 'O-Methylisoharnstoffsulfate (technisch)' did not show any mutagenic activity in the Salmonella/mamalian microsome mutagenicity test under the conditions empoyed in this evaluation.

Executive summary:

'O-Methylisoharnstoffsulfate (technisch)' was examined for mutagenic activity in the Ames test using the histidine requiring S. typhimurium mutants TA 1535, TA 1537, TA 98 and TA 100 as indicator strains and a liver microsome fraction of Aroclor-induced rats for metabolic activation.

It was concluded that 'O-Methylisoharnstoffsulfat (technisch)' did not show any mutagenic activity in the Ames test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

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

Link to relevant study records

Reference

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

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

Species:

rat

Strain:

Fischer 344

Key result

Sex:

male/female

Genotoxicity:

positive

Toxicity:

not examined

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (positive)

Additional information

Additional information from genetic toxicity in vivo:

Justification for selection of genetic toxicity endpoint
Allthough test was performed accoring to an old guideline it is reliable.

Justification for classification or non-classification

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.