Registration Dossier

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
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
Cited as Directive 92/69/EEC, B.1 bis
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Triethylenglykoldivinylether, Substance number 96/283
- Analytical purity: ABOUT 98.4 % (GO)
- Physical state: LIQUID, ACHROMATIC, CLEAR
- Lot/batch No.: 3401/95-09
- Stability under test conditions: The stability of the test substance in olive oil DAB 10 for a time period of 4 hours was confirmd by analysis.
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: DR. K. THOMAE GMBH, BIBERACH, Germany
- Age at study initiation: YOUNG ADULT ANIMALS
- Weight at study initiation: 150 - 300 g (+/- 20 % of the mean weight)
- Fasting period before study:
- Housing: single
- Diet (e.g. ad libitum): Kliba-Labordiaet 343, Klingenthalmühle AG Kaiseraugst, Switzerland, ad libitum.
- Water: tap water ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 hrs/12 hrs

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: olive oil DAB 10
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 40 g/100 mL
- Amount of vehicle (if gavage): 5 mL
- Justification for choice of vehicle: The test substance is insoluble in aqua bidest.

MAXIMUM DOSE VOLUME APPLIED:

Doses:
2000 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: recording of signs and symptoms several times on the day of administration, at least once each workday; check for dead or moribund animals was made twice each workday and once on saturdays, sundays and on public holiday;body weight was determined shortly before application (day 0), weekly thereafter and at the end of the study (before fasting period).
- Necropsy of survivors performed: yes, at the last day of the observation period. Withdrawal of food at least 16 hours before killing with CO2; the necropsy with grosspathology examination. Necropsy oof all animals that died before as early as possible.
Statistics:
THE BINOMIAL TEST (SNEDECOR GW, COCHRAN WG (1989), STATISTICAL METHODS, 8TH ED., IOWA STATE UNIVERSITY PRESS/AMES) WAS USED.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: No mortality
Mortality:
No mortality was observed in males and females
Clinical signs:
Males: poor general state: 3 animals (hour 0 - 5); dyspnoea: 3 animals (hour 0 - 5); apathy: 3 animals (hour 0 - 5); staggering: 2 animals (hour 5); ataxia: 3 animals (hour 0 - 4); paresis: 3 animals (hour 0 - 1); piloerection: 3 animals (hour 1 - 5); exsiccosis 1 animal (hour 3 - 5).
Females: impaired general state: 2 animals (hour 4 - 5); poor general state: 3 animals (hour 0 - 5); dyspnoea: 3 animals (hour 0 - 5); apathy: 3 animals (hour 0 - 5); abdominal position 2 animals (hour 5); staggering: 2 animals (hour 4 - 5); ataxia: 3 animals (hour 0 - 4); atonia: 1 animal (hour 0 - 4); paresis: 2 animals (hour 0 - 1); piloerection: 3 animals (hour 1 - 5).
Body weight:
Mean body weight: Males: before application: 181 g; after day 7: 245 g; after day 13: 288 g;
Females: before application: 171 g; after day 7: 202 g; after day 13: 214 g.
Gross pathology:
No pathologic findings in males and females

Applicant's summary and conclusion

Conclusions:
Under the conditions of this study, the LD50 of Triethylenglycoldivinylether after oral application was found to be greater than 2000 mg/kg bw.
Executive summary:

For the investigation of the acute oral toxicity of Triethylenglycoldivinylether, three males and three females Wistar rats received a single oral dose of the test material preparation in olive oil at a dose level of 2000 mg/kg bw. Signs of toxicity noted comprised impaired or poor general state, dyspnoea, apathy, abdominal position, staggering, ataxia, atonia, paresis and exsiccosis. The animals appeared normal 1 day after application. The expected body weight gain was observed in the course of the study. No mortality occurred. No abnormalities were noted at necropsy of animals sacrificed at the end of the study. Under the conditions of this study, the LD50 of Triethylenglycoldivinylether after oral application was found to be greater than 2000 mg/kg bw.