2-Propen-1-aminium, N,N,N-tripropyl-, salt with N-cyanocyanamide (1:1)

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:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Details on test material:

- CAS No.: 1312296-85-7
- Purity: 100.4 g/100 g determined by 1H-NMR-analysis.
- Homogeneity: The test item was homogeneous by visual inspection.
- Storage stability: The stability of the test item under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.
- Storage conditions: Room temperature; under N2
- Physical state/color: Solid/beige

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: animals of comparable weight (± 20% of the mean weight); mean weights: 300 mg/kg bw group 1: 186.3 g; 2000 mg/kg bw group: 166.3 g; 300 mg/kg bw group 2: 166.7 g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: single housing in Makrolon cage, type III
- Diet: VRF1(P); SDS Special Diets Services ad libitum (except during fasting period)
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

(deionized)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 300 mg/kg bw groups: 3 g/100 mL; 2000 mg/kg bw group: 20 g/100 mL
- Justification for choice of vehicle: Solution in deionized water

ADMINISTRATION VOLUME: 10 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: Based on available acute oral toxicity data with sodium dicyanamid (LD50 = 725 mg/kg) the starting dose was chosen to be 300 mg/kg bw.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

300 mg/kg bw: 6 females; 2000 mg/kg bw: 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A check for any dead or moribund animals was made at least once each workday. Clinical signs were recorded several times on the day of administration, and at least once daily thereafter each workday for the individual animals. Individual body weights were determined shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals died in the 2000 mg/kg test group within one day after application. No mortality occurred in both 300 mg/kg test groups.

Clinical signs:

other: In the animals of the 2000 mg/kg bw test group poor general state was noted from hour 1 until hour 3 or 4 after application. In one of these animals impaired general state was noted at hour 0. Dyspnoea and piloerection was noted in all animals beginning w

Gross pathology:

In all animals which died in the 2000 mg/kg test group gaseous stomach, red discoloration of the small intestine and yellowish discoloration of the stomach content were noted at the necropsy. In one of these animals additionally dark spotted discoloration of all lung lobes was noted. In another female additionally red discoloration of the glandular stomach was noted after the animal died.

There were no macroscopic pathological findings in animals sacrificed at the end of the observation period ( 6 females of the 300 mg/kg bw groups).

Any other information on results incl. tables

MORTALITY:

Dose (mg/kg bw):	2000	300	300
Sex:	female	female	female
Administration:	1	1	2
No. of animals:	3	3	3
Mortality (animals):	3	No mortality	No mortality

 

 

MAXIMUM INCIDENCE OF CLINICALSIGNS:

Dose (mg/kg bw):		2000
Sex:		female
Administration:		1
No. of animals:		3
Animal No.:		1	2	3
Abnormalities:
Impaired general state:		-	-	h0
Poor general state:		h1 - h3	h1 - h4	h1 - h4
Dyspnoea:		h1 - h3	h1 - h4	h0 - h5
Piloerection:		h1 - h3	h1 - h4	h0 - h5
Abdominal position:		h1 - h2	-	h3 - h5
Lateral position:		h3	-	-
Extension spasm:		h3	-	h3 - h5
Rolling convulsions:		h1 - h2	h3 - h4	h1 - h2
Tremor:		-	h2	-
Straub phenomenon:		-	-	h3 - h5
Mortality:		h3	h5	d1
Dose (mg/kg bw):		300
Sex:		female
Administration:		1
No. of animals:		3
Animal No.:		1	2	3
Abnormalities:		-	-	-
Dose (mg/kg bw):		300
Sex:		female
Administration:		2
No. of animals:		3
Animal No.:		1	2	3
Abnormalities:
Impaired general state:		h3 - h5	h5	h5
Poor general state:		-	h2 - h4	h2 - h4
Dyspnoea:		h3 - h5	h2 - h5	h2 - h5
Piloerection:		h3 - h5	h2 - h5	h2 - h5
Staggering:		-	h2 - h4	h2 - h4
Tremor:		-	-	h2

 

 

BODY WEIGHT CHANGES:

Individual body weights
Dose (mg/kg bw):	2000					300					300
Administration:	1					1					2
Animal No.:	1	2	3	mean	SD	1	2	3	mean	SD	1	2	3	mean	SD
Body weight at study day (g):
0	166	170	163	166.3	3.51	191	187	181	186.3	5.03	174	158	168	166.7	8.08
1	-	-	156	-		-	-	-	-		-	-	-	-
7	-	-	-	-		203	194	185	194.0	9.00	189	186	196	190.3	5.13
14	-	-	-	-		204	199	196	199.7	4.04	200	199	206	201.7	3.79

 

 

GROSS PATHOLOGY:

Dose (mg/kg bw):	2000			300			300
Administration:	1			1			2
No. of animals:	3			3			3
Animal No.:	1	2	3	1	2	3	1	2	3
Macroscopic pathologic abnormalities:	Stomach: gaseous, content yellowish discolored; small intestine: red discolored	Stomach: gaseous, content yellowish discolored; glandular stomach: red discolored; small intestine: red discolored	Lung: dark spotted discoloration of all lobes; stomach: gaseous, content yellowish discolored; small intestine: red discolored	-	-	-	-	-	-

 

Applicant's summary and conclusion

Interpretation of results:

moderately toxic

Remarks:

Migrated information

Conclusions:

Under the conditions of this study the median lethal dose of the test substance after oral administration was found to be greater than 300 mg/kg bw and less than 2000 mg/kg bw in rats.

Executive summary:

The study was performed according to OECD guideline 423 in compliance with GLP.

 

In this acute oral toxicity study performed according to the Acute Toxic Class method, doses of 2000 and 300 mg/kg bw of the test item (preparations in doubly deionized water) were administered to three test groups of three fasted Wistar rats each (2000 mg/kg bw in 3 females, 300 mg/kg bw in 6 females) by gavage in a sequential manner.

 

The following test substance-related clinical observations were recorded:

- 2000 mg/kg (single test group):

Mortality in all animals, impaired general state in one out of three animals, poor general state in all animals, dyspnoea in all animals, piloerection in all animals, abdominal position in two out of three animals, lateral position in one out of three animals, extension spasm in two out of three animals, rolling convulsions in all animals, tremor in one out of three animals, Straub phenomenon in one out of three animals.

 

- 300 mg/kg (first test group):

No mortality occurred. No clinical signs were observed in the first test group dosed with 300 mg/kg bw.

 

- 300 mg/kg (second test group):

No mortality occurred, impaired general state in all animals, poor general state in two out of three animals, dyspnoea in all animals, piloerection in all animals, staggering in two out of three animals, tremor in one out of three animals.

 

The mean body weight of the surviving animals increased within the normal range throughout the study period.

The following macroscopic pathological findings were observed in the animals that died (2000 mg/kg; 3 females):

Dark spotted discoloration of all lung lobes, yellowish discoloration of the stomach content, gaseous stomach, red discoloration of the glandular stomach, red discoloration of the small intestine.

There were no macroscopic pathological findings in animals sacrificed at the end of the observation period (300 mg/kg; 6 females).

 

Conclusion: The acute oral LD50 was calculated to be LD50, oral, rat > 300 mg/kg < 2000 mg/kg bw.