1,2-dihydro-5-nitro-3H-1,2,4-triazol-3-one

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

26 September 1997 (Received for publication)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test has not been performed to GLP standards and no guideline required.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1998

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Metabolism of 14C-NTO in vitro in rat liver microsomes.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,2-dihydro-5-nitro-3H-1,2,4-triazol-3-one

EC Number:

213-254-4

EC Name:

1,2-dihydro-5-nitro-3H-1,2,4-triazol-3-one

Cas Number:

932-64-9

Molecular formula:

C2H2N4O3

IUPAC Name:

1,2-dihydro-5-nitro-3H-1,2,4-triazol-3-one

Test material form:

solid: crystalline

Details on test material:

- Name of test material : 3-NITRO-1 ,2,4-TRIAZOL-5-0NE (NTO)
- Substance type: energetic explosive
- Physical state: light green to white crystalline solid with no odor
- Purity ca.99%

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

Rat liver microsomes were harvested from the livers of the rats which had been pre-treated with either phenobarbital, 3-methylcholanthrene, dexamethasone or clofibrate.

Administration / exposure

Details on exposure:

Anaerobic incubations were performed by bubbling argon over the phosphate buffer for 1 hour, microsomal suspensions and NTO and NADPH - generating system were added. Incubations were also performed in the presence of oxygen in the same manner but without the argon deaeration stage. Reactions were stopped and samples concentrated and analysed by HPLC.

Results and discussion

Main ADME results

Type:

metabolism

Results:

Nitroreduction of NTO was principally catalysed by the microsomal fraction of rat liver cells. This reaction required a NADPH-generating system and led to the formation of two metabolites, 5-amino-1,2,4-triazol-3-one 2 and 5-hydroxy-1,2,4-triazol-3-one 3.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

The amounts of metabolites (ATO and urazole were determined by monitoring the radioactivity of the HPLC effluent, and are reported as a percentage of the initial C-NTO radioactivity.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: No bioaccumulation tested .
The reported results indicate that NTO is metabolized by liver microsomes via two distinct pathways. The first reaction is the nitroreduction of NTO, which is the only reaction that occurs in anaerobiosis. In contrast with reported results, nitroreduction is only partially inhibited by oxygen.
The second reaction leads to the formation of urazole via the oxidative denitrification of NTO.