Registration Dossier

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

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals 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:
no data
Control animals:
not specified
Positive control:
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.

Applicant's summary and conclusion