Methylurea

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

Studies in the guinea-pig stomach on the formation of N-nitrosomethylurea, from methylurea and sodium nitrite, and its disappearance.

Author:

Yamamoto M

Year:

1987

Bibliographic source:

Food Chem Toxicol. 25 (9) :663-8

Materials and methods

Objective of study:

metabolism

Principles of method if other than guideline:

The formation of N-nitrosomethylurea (NMU) from methylurea (MU) and sodium nitrite in the guinea-pig stomach and the disappearance of NMU from the stomach were studied. Guinea-pigs were used since they have only glandular stomachs and the pH of the gastric juice (1-2) is similar to that of humans.

GLP compliance:

not specified

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 (MU)

Radiolabelling:

no

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Shizuoka Laboratory Animal Center (Shizuoka)
- Age at study initiation: 3 weeks
- Weight at study initiation: 290-370g
- Fasting period before study: from the day before the experiment (but tap-water ad libitum).
- Housing: no data
- Individual metabolism cages: no
- Diet (e.g. ad libitum): RC4, from Oriental Yeast Co. Ltd, Tokyo
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on exposure:

The solutions of NMU (2µmol) or MU (7.5/1tool) and NaNO2 (15µmol) were given orally by stomach tube. In the experiment in which MU and NaNO2 were given, the MU solution was given first followed immediately by the NaNO2 solution. After a defined time interval, the abdominal cavity was
opened and whole blood and the stomach contents were collected and analyzed.

Duration and frequency of treatment / exposure:

Once

Doses / concentrations

Remarks:

Doses / Concentrations:
7.5 µmol MU and 15 µmol NaNO2 were co-injected into the ligated stomach or were given orally.

No. of animals per sex per dose / concentration:

No data

Control animals:

not specified

Details on study design:

- Dose selection rationale: No data
- Rationale for animal assignment (if not random): No data

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: blood, stomach content
- Time and frequency of sampling: 10 and 30 minutes after treatment

METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: stomach content
- Time and frequency of sampling: 10 and 30 minutes after treatment

Statistics:

No data

Results and discussion

Metabolite characterisation studies

Metabolites identified:

not specified

Details on metabolites:

3.1 µmol NMU was detected 10 min after the injection, followed by a gradual decrease. When MU and NaNO2 were given orally to the animals, 0.7-1.0 µmol NMU was detected in the stomach 10 min after the treatment. Thus, according to the authors, NMU was shown to be formed readily in the stomach of the guinea-pig and to be absorbed from the stomach into the blood.