N'-(ethylcarbonimidoyl)-N,N-dimethylpropane-1,3-diamine monohydrochloride

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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N'-(ethylcarbonimidoyl)-N,N-dimethylpropane-1,3-diamine monohydrochloride

EC Number:

247-361-2

EC Name:

N'-(ethylcarbonimidoyl)-N,N-dimethylpropane-1,3-diamine monohydrochloride

Cas Number:

25952-53-8

Molecular formula:

C8H17N3.ClH

IUPAC Name:

N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide hydrochloride

Test material form:

solid

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8 to 11 weeks old
- Weight at study initiation: 162 to 189 g for all animals
- Fasting period before study: No
- Housing: Full barrier in an air-conditioned room. Housed individually in IVC cages including saw fibre bedding.
- Diet (e.g. ad libitum): Free access to Altromin maintenance diet.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): 10 per hour
- Photoperiod (hrs dark / hrs light): Artificial lighting (12 hours light/dark cycles)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Aqua ad injectionem

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/mL or 0.03 g/mL
- Amount of vehicle (if gavage): 10 mL/Kg
- Justification for choice of vehicle: Standard vehicle for test type and chosen based on its non-toxic characteristics.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/Kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: No toxicity data available and accordingly limit dose chosen.

Doses:

The starting dose was selected to be 2000 mg/kg bw. This was then followed by two further doses of 300 mg/kg bw.

No. of animals per sex per dose:

3 females per step (3 at 2000 mg/kg bw and 6 at 300 mg/kg bw)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were weighed on Day 1 (prior to dosing) and days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs were noted on the day of dosing and then once daily during the observation period.

Statistics:

Not applicable to study type

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

500 mg/kg bw

Based on:

test mat.

Mortality:

All animals that received 2000 mg/kg bw were found dead within 3 hours post dose (3/3). During step two (300 mg/kg bw), one animal was found dead 1 day post dose (1/6).

Clinical signs:

other: 2000 mg/kg bw: Signs observed in two animals included recumbency, apathy, ataxia and half-eyelid closure. 300 mg/kg bw: The most relevant signs at this dose (observed in the majority of animals) were piloerection, reduced spontaneous activity, recumbency

Gross pathology:

2000 mg/kg bw: No significant necropsy findings were noted.
300 mg/kg bw: In the animal found dead a bloated stomach, duodenum, jejunum, ileum with Peyer’s patches, mesenteric lymph node, caecum and colon were noted along with a red discolouration of the lung. Red spots in the lung were also observed in another surviving animal and no other significant findings were observed in the groups

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

A reliable, guideline study is available providing an LD50 cut-off value of 500 mg/kg bw to rats.