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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 27 November 2012 to 04 February 2013
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:
2013
Report date:
2013

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
Chemical structure
Reference substance name:
[(±)-(4-amino-2-hydroxy-4-oxobutyl)trimethylammonium] chloride
EC Number:
226-073-0
EC Name:
[(±)-(4-amino-2-hydroxy-4-oxobutyl)trimethylammonium] chloride
Cas Number:
5261-99-4
Molecular formula:
C7H17N2O2.Cl
IUPAC Name:
4-amino-2-hydroxy-N,N,N-trimethyl-4-oxobutan-1-aminium chloride
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Physical state: white powder
- Analytical purity: 99,4%
- Lot/batch No.: WI 2274
- Storage condition of test material: at room temperature not exceeding 40°C.

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: 9-10 week old
- Weight at study initiation: 193-205 g
- Fasting period before study: On the day before the start of the experiment, i.e. about 19 hours before the administration of the test item, the food was withheld but the water was still available.
- Housing: The animals were kept in plastic cages covered with wire bar lids. The dimensions of the cages were as follows: 58 x 37 x 21 cm (length x width x height). In the sighting study, the animal was caged individually, whereas in the main study, there were four animals per cage.
- Diet (e.g. ad libitum): “Murigran” standard granulated laboratory fodder, ad libitum
- Water (e.g. ad libitum): drinking tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 – 22 °C
- Humidity (%): 38 – 70%
- Air changes (per hr): about 16 times/hour
- Photoperiod (hrs dark / hrs light): 12 hours light – 12 hours dark

IN-LIFE DATES: From: 30 November 2012 To: 14 December 2012

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 0.5 mL/100 g of animal body weight

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The evaluation of general condition of the animals, i.e. the observation of all animals for morbidity and mortality was conducted twice a day or once a day (on days off) during the 14-day period of the experiment. The detailed clinical observations were performed on the day of the test item administration (day 0), i.e. 10, 30 and 60 minutes after the administration and then at hourly intervals up to 5 hours. From the 1st to the 14th day of the observation period, the detailed clinical observations were made once a day. The animals’ body weight was determined individually directly before the administration of the test item (day 0) and then on the 7th and 14th day.
- Necropsy of survivors performed: yes
After the 14-day observation period, all animals which survived the experiment were killed by an intraperitoneal administration of morbital at a dose of 200 mg/kg b.w. and subjected to the post mortem examination.

Results and discussion

Preliminary 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, some signs of toxicity were visible on the administration day. These included a slight decrease in locomotor activity, dejection and a bristled coat – from the 1st to the 5th hour after the administration. On 1st and 2nd day after the administration, the animal’s gait was wavering. The animal survived the 14-day observation period. During the entire experiment, the animal’s body weight increased. The animal necropsy did not reveal any pathological changes.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
other: 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, no clinical signs were observed in these animals. All animals survived the 14-day observation period.
Gross pathology:
The animal necropsy did not reveal any pathological changes.

Any other information on results incl. tables

Table 1:    Summary of acute oral toxicity

Females

Dose

Mortality

2000 mg/kg bw

0/5

Applicant's summary and conclusion

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

The acute oral toxicity study – fixed dose procedure, according to the OECD Guideline No. 420 / EU Method B.1.bis, was performed in order to obtain information on health hazards likely to arise from a single oral exposure caused by the consumption of the test item. The experiment commenced with a sighting study in which the test item at a single dose of 2000 mg/kg b.w was administered to one animal. On the grounds of the sighting study results, four animals used in the main study were given the test item at a dose of 2000 mg/kg b.w. (the animal of the sighting study was included in the main study). After the administration of the test item, the animals were observed for 14 days. General and detailed clinical observations were conducted daily during the entire experiment. The animals’ body weight was determined individually on day 0 (directly before the administration of the test item) as well as on the 7th and 14th day.

After the 14-day observation period, all animals which survived the experiment were euthanized and subjected to a necropsy and a detailed gross examination. Following a single administration of the test item at a dose of 2000 mg/kg b.w. to one animal, some signs of toxicity were observed. The animal survived the 14-day observation period. Following a single administration of the test item at a dose of 2000 mg/kg b.w. to the next four animals used in the main study, no clinical signs were observed during the 14-day observation period. All animals survived the observation period. Body weight gains were stated in all animals. The animal necropsy did not reveal any pathological changes. The oral LD50 for the test substance was greater than 2000 mg/kg bw.