N-nitro-N-(3-methyl-3,6-dihydro-2H-1,3,5-oxadiazin-4-yl)amine

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: expert statement

Adequacy of study:

key study

Study period:

1999-04-09

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No gudieline-conform study. Two-pages expert statement prepared by the former notifier Novartis Crop Protection AG, Basel.

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

expert statement / review summary based on available study results.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

431-060-1

EC Name:

-

Cas Number:

153719-38-1

Molecular formula:

Hill formula: C4H8N4O3 CAS formula: C4H8N4O3

IUPAC Name:

3-methyl-N-nitro-3,6-dihydro-2H-1,3,5-oxadiazin-4-amine

Details on test material:

not applicable

Radiolabelling:

no

Test animals

Species:

other: not applicable

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not applicable

Administration / exposure

Route of administration:

other: not applicable

Vehicle:

other: not applicable

Details on exposure:

not applicable

Duration and frequency of treatment / exposure:

not applicable

Doses / concentrations

Remarks:

Doses / Concentrations:
not applicable

No. of animals per sex per dose / concentration:

not applicable

Control animals:

other: not applicable

Positive control reference chemical:

not applicable

Details on study design:

not applicable

Details on dosing and sampling:

not applicable

Statistics:

not applicable

Results and discussion

Preliminary studies:

not applicable

Toxicokinetic / pharmacokinetic studies

Details on absorption:

In animals CA2343A is assumed to be absorbed rapidly from the gastrointestinal tract into the systemic circulation. The extent of absorption will probably be reasonable to well.

Details on distribution in tissues:

Degradation is assumed to take place with a significant amount of unchanged compound excreted. Rapid and almost complete excretion of CA 2343 A together with its metabolites is espected, mainly via the urine, and as a consequence tissue residues will be low. Therefore no retention and accumulation of CA 2343 A and/or its metabolites is assumed.

Details on excretion:

Degradation is assumed to take place with a significant amount of unchanged compound excreted. Rapid and almost complete excretion of CA 2343 A together with its metabolites is espected, mainly via the urine, and as a consequence tissue residues will be low. Therefore no retention and accumulation of CA 2343 A and/or its metabolites is assumed.

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

Cleavage of the oxadiazine ring to the corresponding nitroguanidine compound is anticipated to be the major metabolic reaction (1) (see figure in the attached original expert statement). Expected minor reactions are hydrolytic and/or oxidative cleavage of the guanidine group to the corresponding urea (2), demethylation of the guanidine group to the corresponding desmethyl compound (3), and cleavage of the nitroguanidine group yielding a
guanidine derivative (4), most probably via short living intermediates like hydroxylamine- and hydrazine-derivates.
The short living intermediates are probably prone to acylation. Most of the metaholites are expected to be the result of more than one of the above reactions. Cleavage of the oxadiazine ring gives rise to minor transformations proceeding rapidly to small molecules and ultimately to CO2. The small
molecules may enter, at least partially, the general metabolism.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
No retention and accumulation of CA 2343 A and/or its metabolites is assumed.

Executive summary:

The purpose of this expert statement was to prepare a toxicokinetic assessment of test substance CA 2343 (oxadiazinamine). For preparing the toxicokinetic assement no specific guideline was followed, the expert statement primarily is based on summarizing the results from availble studies. Some details on absorption and excretion of the test substance, as well as on its assumed metabolites are given in the report. In conclusion, no retention and accumulation of CA 2343 A and/or its metabolites is assumed.