Reaction products of imine and acrylate

Acute Toxicity: dermal

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

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

Test material

Test material information

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:

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

Administration / exposure

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.

Results and discussion

Effect levels

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.

Applicant's summary and conclusion

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.