N,N'-bis(1,3-dimethylbutylidene)-2,2'-iminobis(ethylamine)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in accordance with generally accepted scientific principles, although with incomplete reporting or methodological deficiencies. This reference does not provide a full report with regard to the methods used in this study. Most basic key information is reported.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Standard FHSA procedures

Deviations:

not specified

Principles of method if other than guideline:

Groups of fasted rats were administered a single oral dose of the undiluted test material and observed for 14 days.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N'-bis(1,3-dimethylbutylidene)-2,2'-iminobis(ethylamine)

EC Number:

234-205-3

EC Name:

N,N'-bis(1,3-dimethylbutylidene)-2,2'-iminobis(ethylamine)

Cas Number:

10595-60-5

Molecular formula:

C16H33N3

IUPAC Name:

N-(1,3-dimethylbutylidene)-N'-{2-[(1,3-dimethylbutylidene)amino]ethyl}ethane-1,2-diamine

Test material form:

other: watery liquid

Details on test material:

- Physical details: light amber, watery liquid with a highly noticeable odour
- Storage conditions: ambient room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 204 to 307 g
- Fasting period before study: Yes, 16 to 20 hours
- Diet (e.g. ad libitum): ad libitum Wayne diet
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

1.0, 2.0 and 4.0 mL/kg

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and bodyweight

Statistics:

LD50 is calculated by probit transformation based on 14 days’ observation.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1.88 mL/kg bw

Based on:

test mat.

95% CL:

1.56 - 2.27

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

2.13 mL/kg bw

Based on:

test mat.

95% CL:

1.52 - 3.01

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

1.64 mL/kg bw

Based on:

test mat.

95% CL:

1.17 - 2.31

Mortality:

Mortality data is summarised in Table 1.

In the 4.0 mL/kg dose group, all animals died. Of the male animals, 3 died within 4 hours of dosing with the remaining 2 dying 1 day after dosing. All female animals died on the day of dosing, 4 within 1 hour.

In the 2.0 mL/kg dose group, 2 male and 4 female animals died. Of the males, 1 died 1 day after dosing and the other died 2 days after dosing. Of the 4 female animals, a single death occurred on days 3, 4, 7 and 9 after dosing.

Clinical signs:

other: Clinical signs are summarised in Table 1. Animals in the 4.0 mL/kg dose group exhibited languidness and ataxia 5 minutes after dosing. Other signs included depressed respiration and an impaired righting reflex. Animals in the 2.0 mL/kg dose group exhibi

Gross pathology:

Animals dosed at 4.0 mL/kg exhibited congestion of the lungs, liver, spleen, stomach, and small intestines. Congestion of the left kidney was seen in 1 animal. Five of the 10 animals exhibited bloody urine in the bladder. Diffuse white opacity inside the right eye was seen in 2 animals. Dilation of the right renal pelvis was seen in 2 of the 10.

Animals dosed at 2.0 mL/kg that died exhibited congested lungs, dark red liver and a stomach that was distended and hemorrhagic. Opacities inside one or both eyes were seen in 3 animals, and dark red eyes were seen in 2.
Gross pathology seen in the animals that survived to the end of the observation period were the stomach, liver, and spleen adhered to left abdominal wall, thickened stomach walls and partial atelectasis of lungs. A light-coloured, mottled liver was seen in 1 animal.

In the animals that were dosed at 1.0 mL/kg, 3 of the 10 exhibited the stomach adhered to the liver, spleen or diaphragm. One animals showed dilation of the right renal pelvis, however hydronephrosis is a common finding in this strain of rat.

Any other information on results incl. tables

Table 1 Summary of Mortality and Clinical Signs

Dosage (mL/kg)	Sex	No. of Deaths / No. Dosed	Days to Death	Weight Change in 14 Days (g)	Clinical Signs
4.0	Male	5/5	0, 0, 0, 1, 1	-	Languidness and ataxia in 5/5 at 5 min. Death of 3/5 within 4 hours. Languidness, ataxia, depressed respiration, and impaired righting reflex in 3/3 at 3 hours.
	Female	5/5	0, 0, 0, 0, 0	-	Languidness and ataxia in 5/5 at 5 min. Death of 4/5 within 1 hour. Languidness, ataxia, depressed respiration, and severely impaired righting reflex in 1/1 at 3 hours.
2.0	Male	2/5	1, 2	-76, +65, +66	Languidness, ataxia, injected corneal blood vessels, lacrimation, urine stains, squinting and miosis at 1 day. Hunched appearance, chromodacryorrhea, dark red eyes and thinness from 3 to 14 days.
	Female	4/5	3, 4, 7, 9	+36	Ataxia, languidness, urine stains, injected corneal blood vessels, hunched appearance, chromodacryorrhea, and miosis at 1 day. Pilo-erection, dark red eyes, bloody nose and rigid, erect tail (1/4) at 3 days. Languidness, thinness, dark red eyes, and pilo-erection from 4 to 9 days.
1.0	Male	0/5	-	+58 to +87 (Mean +74.2)	Nothing abnormal.
	Female	0/5	-	+22 to +52 (Mean +37.4)	Congestion of iridial blood vessels in 2/5 at 3 hours.

 

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study, the LD50 in the Albino rat was determined to be 1.88 mL/kg, 95 % confidence limits 1.56 to 2.27 mL/kg.

Executive summary:

The acute peroral toxicity of the test material to the Albino rat was investigated in accordance with standard FHSA procedures.

Groups of five male and five female fasted rats were dosed with the undiluted test material at 4.0, 2.0, and 1.0 mL/kg and observed for 14 days.

All animals dosed at 4.0 mL/kg died within one day of dosing; gross necropsy of these animals revealed congestion or haemorrhage in most of the pleural and abdominal viscera. Six of the animals dosed with 2.0 mL/kg died within 9 days of dosing.

All survivors exhibited signs of distress and bodyweight gain below normal for animals of this age.

Under the conditions of this study, the LD50 in the Albino rat was determined to be 1.88 mL/kg, 95 % confidence limits 1.56 to 2.27 mL/kg.