Reaction products of imine and acrylate

Endpoint summary

Description of key information

Acute oral toxicity:
Key study: OECD Guideline 420 and EU method B.1 bis. GLP study. 
The oral LD50 value was determined to be greater than 2000 mg/kg bw.
Acute dermal toxicity:
Key study: OECD Guideline 402 and EU method B.3. GLP study. 
The dermal LD50 value was determined to be greater than 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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.

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

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

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch 1 and the study was carried out in accordance with internationally valid GLP principles.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Germany
- Age at study initiation: Five 8-week-old males and five 10-week-old females were used in the experiment.
- Weight at study initiation: Five males with the average body weight of 292.6 g and five females with the average body weight of 268.4 g were used in the experiment.
- Housing: The rats will be kept in cages with a plastic bottom and wire bar lids. The dimensions of the cages will be as follow: (length x width x height) 58 x 37 x 21 cm. UV-sterilized wood shavings will be used as bedding. Following the administration of the test material on the animals’ skin, each one will be kept individually in one cage. After the removal of the test material from the animals’ skin, i. e. on the following days of the experiment, the rats will be kept at five per cage, each sex separately.
- 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): 20-22 °C
- Humidity (%): 40 – 70%
- Air changes (per hr): 12 hours light – 12 hours dark

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 30-45cm2
- % coverage: 10%
- Type of wrap if used: The test item will be applied evenly to gauze patches moistened with a few drops of water and then laid on the prepared skin. The gauze patches will be covered with PVC foil and then, an elastic bandage will be used to make a circular band protecting the patch and the test item.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The residual test item will be removed using water.
- Time after start of exposure: The test item will be in contact with skin for 24 hours.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex 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 the animals, i.e. the observation of all animals for mortality and morbidity will be conducted twice a day and once a day (on days off). After the administration of the test item, detailed clinical observations will be performed at hourly intervals on the administration day (day 0) up to the 5th hour. 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 in 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 before killing the animals.

- Necropsy of survivors performed: yes
The rats which die spontaneously during the experiment will be subjected to a gross necropsy. All rats which survive the period of the experiment will be humanely killed after a 14-day observation period by a peritoneal 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 cavities with their content will be performed at necropsy.

Sex:

male/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:

Following a single application of the test item, the animals did not show any general clinical signs.

Body weight:

After the 14-day observation period, all animals’ body weight increased.

Gross pathology:

During the gross examination no pathological changes were observed in the animals.

Other findings:

No pathological changes on the animals’ skin in the site of the test item application were observed.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

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

Executive summary:

The acute dermal toxicity study will be conducted in compliance with the OECD Guideline for the Testing of Chemicals No. 402 (1987): Acute dermal toxicity and the EU Method B.3.: Acute toxicity (dermal).

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

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch 1 and the study was carried out in accordance with internationally valid GLP principles.

Additional information

Acute oral toxicity:

Key study: OECD Guideline 420 and EU method B.1 bis. GLP study.

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

Acute dermal toxicity:

Key study: OECD Guideline 402 and EU method B.3. GLP study.

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

Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

Based on the available data, the substance is not classified for acute toxicity:

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

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