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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-09-06 until 1995-10-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline-conform study under GLP without deviations.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

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:

- Name of test material (as cited in study report): CA 2343 A (Intermediate of CGA 293343)
- Substance type: monoconstituent organic substance
- Physical state: solid
- Analytical purity: 96.7 %
- Impurities (identity and concentrations): no data
- Purity test date: no data
- Lot/batch No.: P.503005
- Expiration date of the lot/batch: Date of reanalysis: December 1996
- Stability under test conditions: not reported
- Storage condition of test material: 0 - 5 °C

Test animals

Species:

rat

Strain:

other: albino rats (Tif: RAI f (SPF))

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, Stein / Switzerland
- Age at study initiation: "young adult rats", acc. to the study report
- Weight at study initiation: 174 to 217 g
- Fasting period before study: Prior to dosing, the animals were fasted overnight.
- Housing: The animals were housed in Macrolon cages type 4, with standardized soft wood bedding
- Diet (e.g. ad libitum): Rat diet (NAFAG 890, NAFAG, Gossau/SG, Switzerland) ad libitum.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Rats were acclimatized at least for 5 days before administration.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 55 ± 10 %
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour/day light cycle


IN-LIFE DATES: From: 1995-09-12 To: 1995-10-04

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80
- Amount of vehicle (if gavage): 10 ml/kg body weight
- Justification for choice of vehicle: no justification given
- Lot/batch no. (if required): not reported
- Purity: not reported


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body weight


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: not applicable

Doses:

1000 and 2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations for mortality, weighing immediately before administration and on days 7 and 14
- Necropsy of survivors performed: Spontaneously dying animals were submitted to a gross necropsy as soon as possible; survivors at the end of the observation period.
- Other examinations performed: clinical signs, body weight: daily for 14 days

Statistics:

no statistics applied

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

approximate LD50

Effect level:

>= 1 000 - <= 2 000 mg/kg bw

Mortality:

At 2000 mg/kg, 3 of 5 males and all females were found dead within 7 hours after administration of the test article. At 1000 mg/kg, all animals survived to the scheduled sacrifice.

Clinical signs:

other: In-life observations indicating treatment related systemic effects such as dyspnea, reduced locomotor activity, convulsions, hunched posture and piloerection were recorded in both sexes at 2000 mg/kg. Tremor, ataxia, diarrhea and ventral recumbency were l

Gross pathology:

At necropsy, no deviations from normal morphology were found in all animals.

Other findings:

not applicable

Any other information on results incl. tables

Tab. 1: Mortality data

Dose group	No. of deaths	% deaths	Animal No./died: time after administration  (h = hours, d = days)
Males
1000 mg/kg	0 / 5	0
2000 mg/kg	3 / 5	60	4 (2h), 1 (7h) 5 (Id)
Females
1000 mg/kg	0 / 5	0
2000 mg/kg	5 / 5	100	1 (4h), 2 - 4 (5h), 5 (Id)

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The LD50 in rats of both sexes was approximately determined to be greater than 1000 but lower than 2000 mg/kg body weight. Based on this study result, acc. to the new OECD classification system for chemicals CA 2343 would be classified as category 4 concerning its acute oral toxic effects.

Executive summary:

The purpose of this study was to evaluate the oral acute toxicity of test item CA 2343 (oxadiazinamin; intermediate of CGA 293343), acc. to OECD Guideline 401. Upon single dose, oral administration of 1000 and 2000 mg/kg to male and female rats and a 14 day post-treatment observation period, the following LD50 was determined . At 2000 mg/kg CA 2343 A elicited evident signs of acute toxicity and mortality in male and female rats. Signs of acute toxicity, but no mortality, were seen after treatment with 1000 mg/kg. Therefore the LD50 in rats of both sexes was approximately determined to be greater than 1000 but lower than 2000 mg/kg body weight. Based on this study result, acc. to the new OECD classification system for chemicals CA 2343 would be classified as category 4 concerning its acute oral toxic effects.