Registration Dossier

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

Referenceopen allclose all

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 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

Reference
Name:
Unnamed
Type:
Constituent
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 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

Applicant's summary and conclusion