Methylurea

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment.

Data source

Reference

Reference Type:

publication

Title:

Inhibition of mouse testicular DNA synthesis by mutagens and carcinogens as a potential simple mammalian assay for mutagenesis.

Author:

Friedman MA and Staub J

Year:

1976

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

Test material information

Constituent 1

Reference substance name:

Methylurea

EC Number:

209-935-0

EC Name:

Methylurea

Cas Number:

598-50-5

Molecular formula:

C2H6N2O

IUPAC Name:

methylurea

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.