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
Year:
2005
Report date:
2005

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Glycerol, ethoxylated, esters with acrylic acid
EC Number:
500-322-6
EC Name:
Glycerol, ethoxylated, esters with acrylic acid
Cas Number:
144086-03-3
Molecular formula:
UVCB substance
IUPAC Name:
[(uraniovanadio)methyl]borane
Details on test material:
- Name of test material (as cited in study report): Glycerin3EOTA
- Analytical purity: >99 %
- Lot/batch No.: GK0561/160
- Stability under test conditions: The stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Strain 1HanRcc:WIST(SPF) from RCC Ltd, Switzerland
- Age at study initiation: Young adult animals (female animals approx 8 - 12 weeks)
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: Single housing in stainless steel wire mesh cages
- Diet (e.g. ad libitum): Kliba-Labordiaet (Maus / Ratte Haltung "GLP"), Provimi Kliba SA, Switzerland
- Water (e.g. ad libitum): Tap water
- Acclimation period: at least 5 days


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

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 6 or 40 g/100mL
- Justification for choice of vehicle: Olive all Ph.Eur./DAB had to be used to ensure homogeneity of the preparation


MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg
Doses:
300, 2000 mg/kg bw
No. of animals per sex per dose:
3 females received 2000 mg/kg bw; 6 females received 300 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing
Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter and at the end of the study. Additionally, at day of death in animals that died or were sacrificed moribund starting with study day 1.
Signs and symptoms: Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual
animals.
Mortality: A check for any dead or moribund animal was made twice each workday and once an Saturdays, Sundays and on public holidays.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Mortality:
300 mg/kg bw: 0/6 animals
2000 mg/kg bw: 3/3 animals within the first two days
Clinical signs:
No clinical observations were observed during clinical examination in the 300 mg/kg administration group.
Clinical observation in the 2,000 mg/kg administration group revealed poor general state, dyspnoea, staggering and piloerection and were observed in two females one day after administration.
Body weight:
The mean body weights of the administration groups increased throughout the study period.
Gross pathology:
Animals that died (2000 mg/kg bw)
Moderate or severe, (red) hyperemia in the glandular stomach (3 females); slight, red discoloration of contents of the small intestine (1 female);
black discoloration of contents of the small intestine (1 female)

Surviving animals (300 mg/kg bw)
No macroscopic pathologic abnormalities were noted at termination of the study.

Applicant's summary and conclusion