Registration Dossier

Diss Factsheets

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: OECD guideline and EU method. GLP study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Reaction products of imine and acrylate
Molecular formula:
Not applicable. UVCB substance
IUPAC Name:
Reaction products of imine and acrylate
Details on test material:
- Physical state: amber, clear liquid
- Lot/batch No.: 3017/20495
- Storage condition of test material: in cool, airy places away from strong alkalies, acids, ignition sources, direct sunlight.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Germany
- Age at study initiation: One 10-week-old female was used in the sighting study. Four 11-week-old females were used in the main study.
- Weight at study initiation: One female weighing 200 g was used in the sighting study. Four females with the average body weight of 207 g were used in the main study.
- Fasting period before study: The animals will be starved for 18 hours prior to the administration of the test item.
- Housing: The rats will be kept in plastic cages with a wire bar lids and the following dimensions: (length x width x height) 58 x 37 x 21 cm. UV-sterilized wood shavings will be used as bedding.
- Diet (e.g. ad libitum): standard granulated fodder “Murigran", ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23 °C
- Humidity (%): 40 – 70%
- Air changes (per hr): 12 hours light – 12 hours dark
- Photoperiod (hrs dark / hrs light): about 16 times/hour

Administration / exposure

Route of administration:
other: oral: The test item at a single dose will be given to the stomach of the animal with the aid of a ball ended feeding needle affixed to the top of a syringe.
Vehicle:
water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: For all tested doses, the test item will be given in the form of an aqueous solution in a constant volume but at different concentrations. The volume of the aqueous solution given once to the animals will be equal to 0.5 mL/100 g b.w.

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The evaluation of a general condition of animals, i.e. the observation of all animals for morbidity and mortality will be conducted twice a day or once a day on days off. Detailed clinical observations taking place on the administration day (day 0) will be performed 10, 30 and 60 minutes after the administration and then at hourly intervals – up to the 5th hour after the administration. From the 1st to the 14th day of the observation period detailed clinical observations will be performed once a day. The observations will comprise: changes of the skin, hair, eyes and mucous membranes, respiratory system, circulatory system, autonomic and central nervous system, somatic activity and behavior.

Body weight of the animals will be determined individually for each animal directly before the administration of the test item (day 0) and then on the 7th and the 14th day.

- Necropsy of survivors performed: yes.
All rats which die spontaneously during the experiment will be subjected to a gross necropsy. The rats which survive the experiment will be killed after a 14-day observation period by the intraperitoneal administration of morbital at a dose of 200 mg/kg b.w. and subjected to a post mortem examination. A detailed gross examination of the external body surfaces, all apertures, cranial, thoracic and abdominal cavity with their content will be performed at necropsy.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived the period of the experiment.
Clinical signs:
Sighting study
Following a single administration of the test item at a dose of 2000 mg/kg b.w. to one animal used in the sighting study, one stated some signs of toxicity; however, they were visible only on the administration day.

Main study
Following a single administration of the test item at a dose of 2000 mg/kg b.w. to four animals used in the main study, one stated some signs of toxicity; however, they were visible only on the administration day.
Body weight:
During the whole experiment all animals’ body weight increased.
Gross pathology:
The gross examination did not reveal any pathological changes in the animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value was determined to be greater than 2000 mg/kg bw.
Executive summary:

The acute oral toxicity study – fixed dose procedure will be conducted in compliance with the OECD Guideline for the Testing of Chemicals No 420 (2001): “Acute oral toxicity – fixed dose procedure” and EU Method B.1.BIS.: “Acute oral toxicity – fixed dose procedure”.

A group of five Sprague-Dawley female rats was exposed orally to a dose level of 2000 mg/kg bw. All animals survived the period of the experiment.

The oral LD50 value was determined to be greater than 2000 mg/kg bw.