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Additional toxicological data

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additional toxicological information
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment.

Data source

Reference Type:
Inhibition of mouse testicular DNA synthesis by mutagens and carcinogens as a potential simple mammalian assay for mutagenesis.
Friedman MA and Staub J
Bibliographic source:
Mutat Res 37: 67-76

Materials and methods

Type of study / information:
chemoprevention (inhibition of mutagenicity)
Principles of method if other than guideline:
Male mice were treated orally with NaNO2 either alone or in combination with methylurea. Three hours after treatment, each mouse received [³H]thymidine and was killed 30 minutes later. The testes were removed and homogenized. DNA synthesis was determined as potential indicator in drug evaluation.

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Details on test material:
- Name of test material (as cited in study report): methylurea
- no data on purity of the compound

Results and discussion

Any other information on results incl. tables

Sodium nitrite and methylurea, when administered alone, induced a slight  inhibition of [3H]thymidine uptake, but not statistically significant  from the control.
However, when administered in combination, both chemicals induced significant inhibition of [3H]thymidine uptake.
Combinations of methylurea (2000 mg/kg) and sodium nitrite (150 mg/kg) administered p.o. resulted in gastric synthesis of nitrosomethylurea and inhibited testicular DNA synthesis by 83%. Combinations of methylurea and sodium nitrite of 1000 and 100 mg/kg respectively inhibited DNA synthesis by 75%.
The non-carcinogenic sodium nitrate (NaNO3) in combination with methylurea had no statistically significant effect.

According to the authors, the importance of inhibition of thymidine uptake as a toxic function of carcinogenic or mutagenic chemicals is difficult to interpret.
This response may not be a mutagenic event but a cytotoxic one. However, since all test substances were active acutely, there also appears to be an S-phase component to their toxicity.

Applicant's summary and conclusion