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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August - October 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study; documentation sufficient for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Remarks:

This study was performed in compliance with Good Laboratory Practice (GLP) in Switzerland, Procedures and Principles, March 1986, issued by the Federal Department of the Interior and the Intercantonal Office for the Control of Medicaments, Switzerland.

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

431-060-1

EC Name:

-

Cas Number:

153719-38-1

Molecular 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)
- Physical state: fine, white powder
- Batch No.: P.503005
- Contents/ Purity: 96.7 %
- Storage condition of test material: 0 - 5 °C
- Test material received: August 16, 1995
- Date of reanalysis: December 1996
- VB: 61580

Test animals

Species:

rat

Strain:

other: 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 adults
- Initial body weight range at study initiation: 213 to 270 g
- Housing: individuals in Macrolon cages type 3 with standardized soft wood bedding (Societe Parisienne des Sciures, Pantin, France)
- Diet: ad libitum (NAFAG 890, NAFAG, Gossau/SG, Switzerland)
- Water: ad libitum
- Acclimation period: at least 5 days before exposure


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 °C
- Humidity (%): 55 +/- 10 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: 0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqeous polysorbate 80

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: 10 % of body surface
- Type of wrap if used: gauze-lined semiocclusive dressing fastened around the trunk with an adhesive elastic bandage


REMOVAL OF TEST SUBSTANCE
- Washing: with lukewarm water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight (equivalent to 4 ml/kg body weight)
- Constant volume or concentration used: yes


VEHICLE
- Concentration (if solution): (0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqeous polysorbate 80)

Duration of exposure:

exposure: 24 hours;
observation period after exposure: 14 days

Doses:

One single dose (2000 mg/kg body weight);
rationale for dose selection: the dose level was selected according to OECD 402 (limit test; single application of at least 2000 mg/kg body weight).

No. of animals per sex per dose:

5 (total number of animals: 10)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations (signs and symptoms): daily for 14 days
- Frequency of observations (mortality): daily; a.m. and p.m. on working days, a.m. on weekends
- Frequency of weighing: immediately before application and on day 7 and 14
- Necropsy of survivors performed: yes, at the end of the observation period

Statistics:

Statistics on body weight changes, see "Remarks on results including tables and figures".

Results and discussion

Preliminary study:

No

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

All animals survived to the scheduled sacrifice.

Clinical signs:

other: There were no in-life observations related to toxicity of the test article after single dose, dermal application. There were no remarkble findings at the application site of all animals. Neither mortality nor body weights were affected by the treatment.

Gross pathology:

At necropsy, no deviations from normal morphology were found.

Other findings:

None.

Any other information on results incl. tables

In-life observations

Time after dermal administration (days)

Animal No.

Observations

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1-5, males

No remarkable findings

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+

+

+

+

+

+

+

+

+

+

+

+

+

+

1-5, females

No remarkable findings

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

  

Local Tolerance, 2000 mg/kg (application site)

Time after dermal administration (days)

Animal No.

Observations

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1-5, males

No remarkable findings

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

1-5, females

No remarkable findings

+

+

+

+

+

+

+

+

+

+

+

+

+

+

+

 

 Body weight and necropsy findings, 2000 mg/kg, males

Animal number	Body weights (g)			*	Gross necropsy findings
	Day 0	7	14
1	270	308	347	TS	No observable abnormalities
2	266	302	335	TS	No observable abnormalities
3	252	296	338	TS	No observable abnormalities
4	257	287	317	TS	No observable abnormalities
5	264	296	330	TS	No observable abnormalities
mean	262	298	333
SD	7.2	7.8	11.1

 

 Body weight and necropsy findings, 2000 mg/kg, females

Animal number	Body weights (g)			*	Gross necropsy findings
	Day 0	7	14
1	213	221	239	TS	No observable abnormalities
2	250	273	265	TS	No observable abnormalities
3	227	234	239	TS	No observable abnormalities
4	228	239	257	TS	No observable abnormalities
5	220	240	251	TS	No observable abnormalities
mean	228	241	250
SD	13.9	19.2	11.4

* TS: terminal sacrifice 

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

At 2000 mg/kg, CA 2343 A (intermediate of CGA 293343) elicited no signs of acute toxicity after single dose, dermal administration in male and female rats.

Executive summary:

In an acute dermal toxicity study (OECD 402, limit test), 10 young adult albino rats (Tif: RAI f (SPF)) of both sexes (5 animals per group) were dermally exposed to CA 2343 A) intermediate of CGA 293343) in 0.5 % (w/v) carboxymethylcellulose (in 0.1 % (w/v) aqueous polysorbate 80) for approximately 24 hours to 10% of body surface area at a dose of 2000 mg/kg bw. Animals then were observed for 14 days.

 

Dermal LD₅₀      Males >2000 mg/kg bw

                         Females >2000 mg/kg bw

                         Combined >2000 mg/kg bw

 

There were no in-life observations related to toxicity of the test article after single dose, dermal application.

There were no remarkble findings at the application site of all animals.

Neither mortality nor body weights were affected by the treatment.

At the autopsy, no deviations from normal morphology were found.