Benzyldimethyl[2-[(1-oxoallyl)oxy]ethyl]ammonium chloride

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 December 13, 2013; Termination of the in-life phase January 23, 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented GLP guideline study on a well characterized test material.

Data source

Reference

Title:

Unnamed

Year:

2014

Report date:

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 (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Benzyldimethyl[2-[(1-oxoallyl)oxy]ethyl]ammonium chloride

EC Number:

256-283-8

EC Name:

Benzyldimethyl[2-[(1-oxoallyl)oxy]ethyl]ammonium chloride

Cas Number:

46830-22-2

Molecular formula:

C14H20NO2.Cl

IUPAC Name:

benzyldimethyl[2-(prop-2-enoyloxy)ethyl]azanium chloride

Constituent 2

Reference substance name:

Benzyldimethyl[2-[(1-oxoallyl)oxy]ethyl]-ammonium chloride

IUPAC Name:

Benzyldimethyl[2-[(1-oxoallyl)oxy]ethyl]-ammonium chloride

Details on test material:

- Name of test material (as cited in study report): Flocryl™ ADAM/BZCL 80%
- Substance type: Organic
- Physical state: Colorless liquid
- Analytical purity: Monomer concentration: 78.6%
- Impurities: Water (>21%)
- Composition of test material, percentage of components: 78.6
- Purity test date: 04.12.2013
- Lot/batch No.: ADBZ 5-47-13-14-D
- Expiration date of the lot/batch: not available
- Stability under test conditions: Stable
- Storage condition of test material: +10°C to +25°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, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: Approx. 8 weeks
- Weight at study initiation: 171 - 180 g
- Fasting period before study: 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 - 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 January 08, 2014 To: Termination of the in-life phase January 23, 2014

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Three animals of one sex (preferably females) are treated at 2000 mg/kg b.w. (first step). If two to three animals die, testing at 300 mg/kg b.w. should be performed. If no to one animal dies, the test item should be retested (second step) with 2000 mg/kg b.w., using three animals of the same sex. If, in this second step, two to three animals die, testing at 300 mg/kg b.w. should be performed. If, in this second step, no to one animal dies, no further testing is necessary.

Doses:

Dose level = 2000 mg/kg b.w.
Administered volume = 1.72 mL/kg b.w.

No. of animals per sex per dose:

Dose level 2000 mg/kg b.w. 3 female animals first step
Dose level 2000 mg/kg b.w. 3 female animals second step

Control animals:

no

Details on study design:

- Duration of observation period following administration: All animals were observed for a period of 14 days.
- 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.
- 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. Changes in weight were calculated and recorded.
At the end of the experiments, all 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 mg/kg bw

Based on:

test mat.

Mortality:

None of the animals died.

Clinical signs:

other: Slightly reduced motility, slight ataxia, slightly reduced muscle tone, slight dyspnoea and pilo-erection in all 6 animals 5 to 60 minutes after administration, slight mydriasis was observed 5 minutes after administration in all 6 animals.

Gross pathology:

No pathological changes were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No-observed-effect level : < 2000 mg Flocryl™ ADAM/BZCL 80%/kg b.w., by oral administration
Dose level with first intolerance reactions : 2000 mg Flocryl™ ADAM/BZCL 80%/kg b.w., by oral administration
Lowest lethal dose level : > 2000 mg Flocryl™ ADAM/BZCL 80%/kg b.w., by oral administration
LD50 : Greater than 2000 mg Flocryl™ ADAM/BZCL 80%/kg b.w., p.o.