Propanenitrile, 2-[bis(cyanomethyl)amino]-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Principles of method if other than guideline:

Acute toxic class method (ATC method) by E. Schlede, U. Mischke, R. Roll, D. Kayser: A national validation study of the acute toxic class method - an alternative to the LD50 test. Arch. Toxicol. 66: 455-470 (1992).

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Name of test material (as cited in study report): MGDN
- Substance type: powder
- Physical state: solid
- Analytical purity: 97.9 %
- Lot/batch No.: GRE 3038/F 535
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

other: Wistar CHBB: THOM (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: DR. K. THOMAE GMBH, BIBERACH, FRG
- Age at study initiation: YOUNG ADULT ANIMALS.
- Weight at study initiation: ANIMALS OF COMPARABLE WEIGHT; (150G - 300G); (+- 20% OF THE MEAN WEIGHT)
- Fasting period before study: THE ANIMALS WERE GIVEN NO FEED AT LEAST 16 HOURS BEFORE ADMINISTRATION, BUT WATER WAS AVAILABLE AD LIBITUM.
- Housing: SINGLE HOUSING.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: ACCLIMATIZATION FOR AT LEAST 1 WEEK.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 -24 DEGREES CELSIUS
- Humidity (%): 30 -70 % FOR RELATIVE HUMIDITY
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.25 G/100 ML (25 mg/kg bw) or 2 G/100 ML (200 mg/kg bw)
- Amount of vehicle (if gavage): 10 ML/KG
- Justification for choice of vehicle: AQUEOUS FORMULATION CORRESPONDS TO THE PHYSIOLOGICAL MEDIUM


MAXIMUM DOSE VOLUME APPLIED: 10 ML/KG



CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no data

Doses:

25 mg/kg and 200 mg/kg

No. of animals per sex per dose:

3 males/3 females at 25 mg/kg bw and 3 males at 200 mg/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: INDIVIDUAL BODY WEIGHTS SHORTLY BEFORE APPLICATION (DAY 0), WEEKLY THEREAFTER AND AT THE END
0F THE STUDY (BEFORE FASTING PERIOD). RECORDING 0F SIGNS AND SYMPTOMS SEVERAL TIMES ON THE DAY OF ADMINISTRATION, AT LEAST ONCE EACH WORKDAY FOR THE INDIVIDUAL ANIMALS. A CHECK FOR ANY DEAD OR MORIBUND ANIMAL WAS MADE TWICE EACH WORKDAY AND ONCE ON SATURDAYS, SUNDAYS AND ON PUBLIC HOLIDAYS.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

NECROPSY AT THE LAST DAY OF THE OBSERVATION PERIOD. WITHDRAWAL OF FOOD AT LEAST 16 HOURS BEFORE KILLING WITH C02; THEN NECROPSY WITH GROSSPATHOLOGY EXAMINATION. NECROPSY OF ALL ANIMALS THAT DIED BEFORE AS EARLY AS POSSIBLE.

Statistics:

not applicable

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

other: Median lethal dose

Effect level:

> 25 - <= 200 mg/kg bw

Mortality:

Dose 1 (25 mg/kg): no mortality.
Dose 2 (200 mg/kg): all three male animals died within 2 hours.

Clinical signs:

Animals from the low dose group showed no clinical signs.
All animals of the high dose group suffered from: Poor general state, dyspnoea, apathy, ataxia, tremor and twitching within two hours after treatment. 2 animals showed piloerection after 1 hour. 1 animal showed salivation after 1 hour.

Body weight:

see table 1: Remarks on results.

Gross pathology:

Sacrificed animals (3 male/3 female): no pathologic findings noted.
Animals that died (3 male): agonal congestion.

Any other information on results incl. tables

Table 1: Mean body weights

Mean body weight	male		female
	25 mg/kg	200 mg/kg	25 mg/kg
day 0	227	188	187
day 7	286		228
day 13	315		241