2-imidazolidone

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Data source

Reference

Reference Type:

publication

Title:

Rat Hepatic Microsomal Metabolism of Ethylenethiourea. Contributions of the Flavin-Containing Monooxygenase and Cytochrome P-450 Isozymes.

Author:

Decker C.J. et al.

Year:

1991

Bibliographic source:

Chem. Res. Toxicol. 4, 482-489

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Microsomes were incubated with ethylenethiourea (ETU) or 2-imidazolidone (EU) ± NADPH and then recovered by centrifugation for the determination of P-450 enzymatic activity.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-imidazolidone

EC Number:

204-436-4

EC Name:

2-imidazolidone

Cas Number:

120-93-4

Molecular formula:

C3H6N2O

IUPAC Name:

2-imidazolidone

Test material form:

solid

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Simonsen Labs, Gilroy, CA
- Weight: 220-250 g

ENVIRONMENTAL CONDITIONS
No data

IN-LIFE DATES: No data

Administration / exposure

Route of administration:

other: not specified

Vehicle:

not specified

Details on exposure:

Sprague-Dawley rats were administered PB (phenobarbital), DEX (dexamethasone), or BNF (ß-naphthoflavone) and liver microsomes were prepared. Protein concentrations were determined by the method of Lowry et al (1951).

Duration and frequency of treatment / exposure:

no data

Doses / concentrations

Remarks:

No data

No. of animals per sex per dose / concentration:

no data

Control animals:

not specified

Positive control reference chemical:

no data

Details on study design:

Biochemical Assays. Microsomal incubations (6.0 mL) contained 1.0 or 2.0 mM ETU or EU, 1-2 mg/mL microsomal protein, 1.5 mM DTPC, and in some cases 1.0 mM NADPH, 5.0 mM GSH, 0.1 mg/mL superoxide dismutase, or 0.5 mg/mL catalase in 0.1 M phosphate buffer, pH 7.4. Reactions were initiated by the addition of NADPH (+NADPH) or buffer (- NADPH) and were incubated at 37 °C for 15 min. For the heat inactivation studies, microsomes were incubated at 37 °C (in the absence of NADPH) for 1 h prior to incubation with ETU.

Results and discussion

Main ADME results

Type:

metabolism

Results:

Under normal physiological conditions, reactive metabolites from EU generated by either flavin-containning monooxygenase (FMO) or cytochrom P-450 are preferentially trapped by endogenous GSH and do not interact with cellular targets.

Metabolite characterisation studies

Details on metabolites:

Under normal physiological conditions, reactive metabolites from EU generated by either FMO or P-450 are preferentially trapped by endogenous GSH and do not interact with cellular targets.

Any other information on results incl. tables

Under normal physiological conditions, reactive metabolites from EU generated by either FMO or P-450 are preferentially trapped by endogenous GSH and do not interact with cellular targets.