2-Propanol, 1,1'-[[3-[(3-aminopropyl)amino]propyl]imino]bis-, N-tallow alkyl derivs.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996-12-31 to 1997-01-14

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-Propanol, 1,1'-[[3-[(3-aminopropyl)amino]propyl]imino]bis-, N-tallow alkyl derivs.

EC Number:

307-276-4

EC Name:

2-Propanol, 1,1'-[[3-[(3-aminopropyl)amino]propyl]imino]bis-, N-tallow alkyl derivs.

Cas Number:

97592-79-5

Molecular formula:

No molecular formula

IUPAC Name:

2-Propanol, 1,1'-[[3-[(3-aminopropyl)amino]propyl]imino]bis-, N-tallow alkyl derivs.

Details on test material:

- Name of test material (as cited in study report): POLYRAM SL
- Physical state: yellow viscous liquid
- Analytical purity: 100 % (expressed in complex substance)
- Certificate of analysis date: 1996/03/04
- Lot/batch No.: 5788
- Expiration date of the lot/batch: 1997/03
- Storage condition of test material: in dark and at room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: IFFA- CREDO (69210 L'ARBRESLE, FRANCE)
- Age at study initiation: about 6 weeks
- Weight at study initiation: between 184g and 212g (males) and 170g and 183g (females)
- Fasting period before study: overnight prior to administration of the test substance
- Housing: 5 animals by sex in polypropylene cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: the test substance was prepared in Carboxymethyl cellulose (0.5%) at concentrations of 100 and 400 mg/mL for the 500 and the 2000 mg/kg bw dose groups respectively.
- Amount of vehicle (if gavage): 5 mL/kg bw for the 500 and the 2000 mg/kg bw dose groups
- Justification for choice of vehicle: solubility
- Lot/batch no. (if required): Cooper Batch B09710
- Purity:

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw

Doses:

2 groups of 10 animals (5 of each sex)
Doses : Group 1 : 500mg/kg
Group 2 : 2000mg/kg
These doses were chosen according to a preliminary "sighting" study performed on a few number of animals.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- The animals were observed daily for 14 days after treatment.
- Mortalities were checked twice a day during all the observation period.
- A clinical examination was carried out one hour after treatment and frequently during the five hours following treatment and then at least once a day for 14 days.
- Body weights of the animals were recorded just prior to treatment (D1) and then on days 3, 7 and 14 after treatment.
- The animals found dead during the test were immediately necropsied.
- At the end of the 14 observation days, surviving animals were sacrified after barbituric anaesthia, then autopsied.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 500 - < 2 000 mg/kg bw

Mortality:

A mortality rate of 70% was induced with the dose of 2000mg/kg. The time of death chiefly occured between 6 hours and 72 hours following treatment. There were no death amongst animals treated at the dose of 500mg/kg (See table 1 in results and discussion free-text for details).

Clinical signs:

other: - At the 500 mg/kg bw dose-level, except a slight piloerection that appeared 30 minutes after the treatment and disappeared in less than 24 hours, no clinical signs were observed. - At the 2000 mg/kg bw dose-level, all the animals showed an important pilo

Gross pathology:

- Necropsy of animals found dead revealed some changes in lungs, liver, kidneys, spleen (congestion), stomach (distension) and intestine (distension).
- Necropsy of the male sacrified on D10 showed stomach adhesions with liver, spleen and abdominal wall and intestine distended with presence of liquid.
- Necropsy of the surviving animals, on day 15, revealed no significant macroscopic abnormality.

Any other information on results incl. tables

Table 1: Mortality at the 500 and 2000 mg/kg bw dose-levels

Dose	Male	Female	Total
500 mg/kg	0	0	0
2000 mg/kg	2/5 (24 hours = Day 2)1/5 (Day 6)1/5 (Day 10)	1/5 (24 hours = Day 2)2/5 (72 hours = Day 4)	7/10 (end of study)

Table 2: Bodyweight of male animals dosed with 500 mg/kg bw

Animal#	4481	4482	4483	4484	4485	Mean	S.D.
D1	206	184	195	198	197	196	7.9
D4	244	218	231	228	238	231.8	9.9
D8	293	259	273	266	277	273.6	12.8
D15	355	316	310	310	330	324.2	19.1
D15 -D1	149	132	115	112	133	128.2	15.1

Table 3: Bodyweight of female animals dosed with 500 mg/kg bw

Animal#	4486	4487	4488	4489	4490	Mean	S.D.
D1	171	180	179	175	170	175	4.5
D4	191	202	199	185	199	195.5	7.0
D8	205	220	222	192	206	209	12.3
D15	202	229	223	210	220	216.8	10.8
D15 -D1	31	49	44	35	50	41.8	8.5

Table 4: Bodyweight of male animals dosed with 2000 mg/kg bw

Animal#	4491	4492	4493	4494	4495	Mean	S.D.
D1	195	196	212	206	189	199.6	9.2
D4	162	159	186	-	-	169	14.8
D8	153	-	158	-	-	155.5	3.5
D15	-	-	250	-	-	250	-
D15 -D1	-	-	38	-	-	38	-

Table 5: Bodyweight of female animals dosed with 2000 mg/kg bw

Animal#	4496	4497	4498	4499	4500	Mean	S.D.
D1	177	175	177	172	183	176.8	4.0
D4	170	-	-	-	168	169	1.4
D8	218	-	-	-	217	217.5	0.7
D15	233	-	-	-	240	236.5	4.9
D15 -D1	56	-	-	-	57	5605	0.7

 

Applicant's summary and conclusion

Interpretation of results:

other: Toxicity category 4 / Harmful

Remarks:

Criteria used for interpretation of results: other: CLP (Reg. 1272/2008/EC) and Directive 67/548/EEC

Conclusions:

Under these experimental conditions, the oral LD50 of the test item was comprised between 500 and 2000 mg/kg in rats.

Executive summary:

The acute oral toxicity of the test item was evaluated in rats according to OECD guideline 401. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.  

The test item was prepared in Carboxymethyl cellulose at 05% and was administered by oral route (gavage), under a volume of 5 mL/kg bw, to groups of five fasted male and female Sprague-Dawley rats. The dose-levels of 500 and 2000 mg/kg bw were selected on the basis of the results obtained in a preliminary sighting study.

In the main study, clinical signs, mortality and body weight gain were checked for a period of up to 14 days following the single administration of the test item. All animals were subjected to necropsy.

At the 500 mg/kg bw dose-level, no mortality occured. A slight piloerection that appeared 30 minutes after the treatment and disappeared in less than 24 hours was the only clinical sign. The body weight gain of the animals was not affected by treatment with the test item and no apparent abnormalities were observed in any animal at necropsy.

At the 2000 mg/kg bwdose-level, 70% (4/5 males and 3/5 females) of the animals died within the study period. Most of the deaths occured 24 to 72 hours after treatment . An important piloerection, a slight abdominal meteorism and a dirty urogenital area were noted in the surviving animals from day 2 to day 8. All animals lost weight at 72 hours but females (not males) recovered at day 8. Necropsy of animals found dead revealed changes in liver, spleen, kidney, lung, intestine and abdominal wall. Necropsies of animals surviving until end of study did not reveal any changes.

Under these experimental conditions, the oral LD₅₀of the test item was comprised between 500 and 2000 mg/kg in rats.