1,1',1'',1'''-ethylenedinitrilotetrapropan-2-ol

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Dissertation: Quadrol, N, N, N', N'-Tetrakis(2-Hydroxypropyl)ethylenediamine: pharmacokinetics and assessment of acute toxicity.

Author:

Dunphy MJ

Year:

1991

Bibliographic source:

Graduate Faculty of the University of Akron

Reference 2

Reference Type:

publication

Title:

Dissertation: Quadrol, N, N, N', N'-Tetrakis(2-Hydroxypropyl)ethylenediamine: pharmacokinetics and assessment of acute toxicity.

Author:

Dunphy MJ

Year:

1991

Bibliographic source:

Dissertation Abstracts International B52/02, 762, Order No. 9119922

Materials and methods

Test guideline

Qualifier:

no guideline available

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,1',1'',1'''-ethylenedinitrilotetrapropan-2-ol

EC Number:

203-041-4

EC Name:

1,1',1'',1'''-ethylenedinitrilotetrapropan-2-ol

Cas Number:

102-60-3

Molecular formula:

C14H32N2O4

IUPAC Name:

1-({2-[bis(2-hydroxypropyl)amino]ethyl}(2-hydroxypropyl)amino)propan-2-ol

Details on test material:

- Name of test material (as cited in study report): Quadrol
- Physical state: viscous fluid
- Analytical purity: >90 %
- Impurities (identity and concentrations): no data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Zivic Miller Laboratories
- Weight at study initiation: 250-300 g
- Housing: separate
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: one week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25
- Humidity (%): 50-60
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

intravenous

Vehicle:

water

Details on exposure:

- Volume of injection: 1 ml
- Side of application: Caudal vein

Doses:

250, 500 mg/kg bw

No. of animals per sex per dose:

10 males

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily for clinical observations and mortalities; on days 2, 7 and 14 for blood and urine analysis
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight, urine analytes (glucose, bilirubin, ketones, protein, blood and pH), plasma analytes (ethylenediamine, +4PO, urea, LDH, creatinine, total protein, glucose, cholesterol, ALT

Statistics:

Results from dosed rats were compared to controls by a two-tailed t-test.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

> 500 mg/kg bw

Mortality:

500 mg/kg bw: 2/10
250 mg/kg bw: 1/10
control: 1/10
There were no immediate deaths following dosing in any group. The animals of the control and 250 mg/kg bw groups died following orbital bleeding. The cause of death appeared to be the ether exposure.

Clinical signs:

Immediately after dosing hyperventilation for typically about 1-2 min, lethargy during the first 1-2 hours post-dose, particularly after the 500 mg/kg bw doses; stool samples usually normal in colour and consistency. Deaths were preceded by bouts of diarrhea and convulsions. All surviving rats were eating, drinking and sleeping normally following 24 hours post-dose.

Other findings:

- Urine analysis: no unusual components, protein, blood, bilirubin, glucose and ketones were negative or trace, the pH was generally in the range of 7-8, which is normal for the SD rat.

- Chlinical chemistry: No test substance-induced variations.

Any other information on results incl. tables

Plasma analytes for acute i.v. dosing:

Dose [mg/kg bw]	Day	n	B. weight [g]	Ethylenediamine, +4PO [mg/ml]	Glucose [mg/dl]	BUN [mg/dl]	Choles. [mg/dl]	LDH [U/l]	Creat. [mg/dl]	T. prot. [g/dl]	ALT [U/l]
Control	pre	10	293±12	n.d.	133±13.9	22±1.5	104±12.5	175±24.5	0.64±0.14	7.7±0.44	46±8.0
	2	10	298±15	n.d.	136±13.5	23±1.2	112±13.6	180±21.8	0.64±0.12	7.4±0.39	43±7.3
	7	10	311±19	n.d.	129±14.8	22±1.6	108±13.3	172±36.4	0.67±0.11	7.7±0.46	48±8.1
	14	9	336±16	n.d.	136±13.1	23±1.2	108±14.1	184±27.9	0.65±0.11	7.8±0.43	45±7.7
250	pre	10	284±11	2.94±0.23	138±14.7	23±1.5	105±16.8	165±21.9	0.64±0.14	7.8±0.48	55±9.7
	2	9	288±12	3.01±0.30	143±16.0	23±1.4	114±16.2	172±21.6	0.65±0.12	7.1±0.67	47±9.6
	7	9	301±17	2.88±0.26	139±13.9	24±1.6	116±13.4	178±26.4	0.66±0.11	7.5±0.46	48±8.6
	14	9	327±18	3.11±0.29	144±18.3	23±1.3	113±14.1	176±32.1	0.65±0.13	7.3±0.54	51±7.7
500	pre	10	290±14	6.87±0.44	145±13.2	22±1.2	119±15.2	177±19.5	0.63±0.11	7.7±0.44	48±9.1
	2	10	290±17	7.03±0.59	131±10.8	23±1.2	114±17.2	189±20.6	0.64±0.11	7.6±0.57	57±4.6
	7	9	299±19	6.65±0.66	136±14.7	24±1.4	125±16.4	188±21.9	0.66±0.12	7.5±0.46	60±7.6
	14	8	321±14	6.78±0.55	140±14.3	23±1.4	123±14.8	175±22.1	0.65±0.13	7.6±0.34	56±6.7

n.d. none detected