[2-(methacryloyloxy)ethyl]trimethylammonium methyl sulphate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Start of the experimental phase: June 10, 2014; Termination of the in-life phase: July 10, 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented GLP guideline study performed on a well identidied test substance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

[2-(methacryloyloxy)ethyl]trimethylammonium chloride

EC Number:

225-733-5

EC Name:

[2-(methacryloyloxy)ethyl]trimethylammonium chloride

Cas Number:

5039-78-1

Molecular formula:

C9H18NO2.Cl

IUPAC Name:

Trimethyl((2-[(2-methylprop-2-enoyl)oxy]ethyl))azanium chloride

Details on test material:

- Name of test material (as cited in study report): FLOCRYL™ MADAM/MECL 75%
- Molecular formula (if other than submission substance):
- Molecular weight (if other than submission substance):
- Smiles notation (if other than submission substance):
- InChl (if other than submission substance):
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type:
- Physical state: Clear to slightly yellow liquid, density 1.11 g/mL
- Analytical purity: Monomer concentration 74.9%
- Impurities (identity and concentrations):
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date: 04.12.2013
- Lot/batch No.: MADC 1-43-13-03-E
- Expiration date of the lot/batch:
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions:
- Storage condition of test material: At room temperature, not stored together with oxidizing and self-igniting products.
- Other:

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, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: Approx. 8 weeks
- Weight at study initiation: 171 - 184 g
- Fasting period before study: Food was offered ad libitum. Feeding was discontinued approx. 16 hours before administration; only tap water was then available ad libitum. After administration of the test item, food had been withheld for a further 3-4 hours.
- Housing: During the 14-day observation period the animals were kept in groups of 3 animals in MAKROLON cages (type III plus).
- Diet (e.g. ad libitum): Food was offered ad libitum. Feeding was discontinued approx. 16 hours before administration; only tap water was then available ad libitum. After administration of the test item, food had been withheld for a further 3-4 hours.
- Water (e.g. ad libitum): Drinking water in bottles was offered ad libitum.
- Acclimation period:At least 5 adaptation days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C (maiximum range).
- Humidity (%): relative humidity of 55% ± 15% (maximum range).
- Air changes (per hr): 15 to 20 times
- Photoperiod (hrs dark / hrs light): The rooms were lit (about 150 lux at approx. 1.50 m room height) and darkened for periods of 12 hours each.


IN-LIFE DATES: From: First dosing June 24, 2014 To: Termination of the in-life phase July 10, 2014

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 2000 mg/kg: tap water, 5000 mg/kg: the test item was used as supplied

Doses:

2 dose level groups: Dose levels 2000 and 5000 mg/kg b.w.
Administration volume 4.50 mL/kg b.w.

No. of animals per sex per dose:

Number of animals 7 female animals; 1 animal at 5000 mg/kg b.w., 6 animals at 2000 mg/kg b.w.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 1 test day and 2 recovery weeks
- Frequency of observations and weighing: Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All surviving animals were observed for a period of 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
During the follow-up period of two weeks, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Observations on deaths were made at least once daily to minimize loss of animals during the study. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study and at death. Changes in weight were calculated and recorded.
At the end of the experiments, all surviving animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded.

Statistics:

No statistical analysis was performed (the method used is not intended to allow a calculation of a precise LD50 value).

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 - < 5 000 mg/kg bw

Based on:

test mat.

Mortality:

2000 mg Flocryl™ MADAM/MECL 75%/kg b.w. : None of the six female animals died prematurely.
5000 mg Flocryl™ MADAM/MECL 75%/kg b.w. : This animal died within 5 minutes after administration.

Clinical signs:

other: 2000 mg Flocryl™ MADAM/MECL 75%/kg b.w. : Slightly reduced motility, slight ataxia and pilo-erection in 6 of 6 female animals, salivation in 4 animals and reddish discoloured lacrimation in 2 animals. 5000 mg Flocryl™ MADAM/MECL 75%/kg b.w. : Slightly red

Gross pathology:

No signs of abnormalities were noted at necropsy at any dose level.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test substance in the rat by the oral route was greater than 2000 mg/kg bw but less than 5000 mg/kg bw.