Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987-04-07 to 1987-05-06
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study, no GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report date:
1987

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-(2-ethoxyethoxy)-2-methylpropane
EC Number:
257-196-8
EC Name:
2-(2-ethoxyethoxy)-2-methylpropane
Cas Number:
51422-54-9
Molecular formula:
C8H18O2
IUPAC Name:
2-(2-ethoxyethoxy)-2-methylpropane

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, 4799 Borchen
- Fasting period before study: 16 hours before administration
- Housing: 1-5 animals in Makrolon Cages Typ III
- Diet: R10 Alleindiät für Ratten, Ssniff Spezialfutter GmbH, 4770 Soest, ad libitum
- Water: Tap water ad libitum
- Acclimation period: 4-8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1 °C
- Humidity (%): 60 % +/- 5 %
- Air changes (per hr): 15 times /hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 6310 mg/kg

DOSAGE PREPARATION: Rats were fasted for 16 hours before application of the test item; administration volume was 3.024-7.602 cm3/kg of undiluted test material.
Doses:
2510, 3160, 3980, 5010 and 6310 mg/kg
No. of animals per sex per dose:
5 males
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Weighing after 1, 7 and 14 days.
- Symptoms: After 6 hours of treatment
- Necropsy of survivors performed: yes
- Other examinations performed: mean values of body weight
Statistics:
LD50 values calculated according to Litchfield and Wilcoxon.

Results and discussion

Preliminary study:
none
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 600 mg/kg bw
Based on:
test mat.
Mortality:
2510 mg/kg: 2 animals
3160 mg/kg: 5 animals
3980 mg/kg: 6 animals
5010 mg/kg: 6 animals
6310 mg/kg: 10 animals
Clinical signs:
After 30 min the animals showed symptoms like sedation, ventral and lateral position, ataxia, shiver, stagger, non controlled movements, squat position, decelerate respiration.

Later symptoms were rough fur, hypothermia, bloody urine, glassy eyes, loud breathing, emaciation, bloody rhinorrhoea and aggressive behavior. In the higher dose groups some animals showed morbidity symptoms after 1 hour. 5 days after application all survived animals were without symptoms.
Body weight:
No abnormalities.
Gross pathology:
Autopsy results:
- Liver and spleen damages
- Bloody urin
- Mucosa was hyperemic
- Red colored stomach content
- Corrosion of stomach mucosa
- White colored pancreas
- Renal pelvis hyperemic
- Dark colored kidneys and dried, hard caecum contents.
- One animal showed smaller abdominal organs, overblown stomach and intestine mucosa, exceeding charge of colon and rectum with dry and hard dung and one clut of blood in the bladder.
- Scared liver
- Color changes of kidneys
- Cirrhosis like changement of the medulla of kidneys
- Swellings on the gastro-oesophageal vestibule
- One animal showed a yellow colored, flattened kidney.
- One animal showed a centre of inflammation on the liver.
- In one animal the diaphragm growed together with stomach, pancreas and melt. Between pancreas and melt was a abscess filled out with sanies.
Other findings:
- Dark color change of the tails and the tail tips.
- Concerned tails were necrotic and of soft consistence. They dried out and droped out after 5-10 days. One animal lost almost the complete tail.

Applicant's summary and conclusion