Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
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:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute 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 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

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- clipping at least 15 hours before study initiation
- Area of exposure: dorsal and dorsolateral parts of the trunk
- % coverage: 50 cm²
- Type of wrap if used: semiocclusive dressing, the bandage consits of 4 layers absorbent gauze (Ph. Eur. Lohmann GmbH & Co.) and fixomull strech (adhesive fleece (beiersdorf AG) for 24 hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Afterwards of removal of the dressing. Rinsing of the appliaction site with warm water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4.04 mL/kg
- Concentration (if solution): undiluted
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
4000 mg/kg
No. of animals per sex per dose:
5
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).
Scoring of skin findings: Individual readings 30 - 60 minutes after removel of the semiocclusive dressing (day 1), weekly thereafter and at the end of the study (Last day of the observation 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:
No statistics were performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 4 000 mL/kg bw
Remarks on result:
other: No mortality
Mortality:
No mortality was observed in males and females.
Clinical signs:
Males: cageside observations: no abnormality; local effects: 2 animals, very slight erythema on day 1;
Females: cageside observations: no abnormality; local effects: 2 animals, very slight erythema on day 2;
Body weight:
Mean body weight: Males: before application: 271 g; after day 7: 292 g; after day 13: 318 g;
Females: before application: 239 g; after day 7: 241 g; after day 13: 251 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 dermal application was found to be greater than 4000 mg/kg bw.
Executive summary:

For the determination of the acute dermal toxicity of Triethylenglycoldivinylether, the test material was applied undiluted at a dose level of 4000 mg/kg bw to the clipped epidermis (dorsal and dorsolateral parts of the trunk) of five male and five female rats and covered by a semi-occlusive dressing for 24 hours. Systemic signs of toxicity were not noted. A very slight erythema was observed in two male and two female animals 1 day after application. No abnormalities were noted at necropsy of animals sacrificed at the end of the study. No mortality occurred. Under the conditions of this study, the LD50 of Triethylenglycoldivinylether after dermal application was found to be greater than 4000 mg/kg bw.