2-Oxazolidinone, 3-ethenyl-5-methyl-

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Justification for type of information:

Characterization of toxicity profile including target organs after 2 weeks exposure to vapors and clarification of further test strategy. Due to low vapor pressure of test substance, only the technically achievable vapor saturation was tested.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The conduct of inhalation exposures will be performed according to the following test guidelines, OECD Guidelines for Testing of Chemicals, Section 4: Health Effects, No. 412, "Repeated Dose Inhalation
Toxicity: 28-day or 14-day Study"

GLP compliance:

no

Test material

Test material information

1

Reference substance name:

3-ethenyl-5-methyl-1,3-oxazolidin-2-one

EC Number:

809-852-5

Cas Number:

3395-98-0

Molecular formula:

C6H9NO2

IUPAC Name:

3-ethenyl-5-methyl-1,3-oxazolidin-2-one

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH Sulzfeld
- Age at study initiation: 9 weeks
- Housing: wire cage, type DK II, singly
- Diet (e.g. ad libitum): Kliba laboratory diet, mouse/rat maintenance “GLP”, 10 mm pellets, Provimi Kliba SA, Kaiseraugst, Basel Switzerland
- Water (e.g. ad libitum): Drinking water ad libitum


DETAILS OF FOOD AND WATER QUALITY:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

The animals were housed singly in wire cages (DK III) that are located in a glass-steel inhalation chambers, V ≈ 200 L. The inhalation atmospheres are passed into the inhalation chambers with the supply air and are removed by an exhaust air system.
Control group: The exhaust air system is adjusted in such a way that the amount of exhaust air is lower than the supply air (positive pressure). This is to ensure that no laboratory room air reaches the control animals.
Test groups 1: The exhaust air system is adjusted in such a way that the amount of exhaust air is higher than the supply air (negative pressure). This is to ensure that no contamination of the laboratory occurs as the result of leakages from the inhalation chambers.

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

6 hours

Frequency of treatment:

each workday (5 times every week), 14 days

Doses / concentrations

Dose / conc.:

18 ppm

Remarks:

saturated vapor concentration

No. of animals per sex per dose:

5 animals

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

Mortality: A check for moribund or dead animals was carried out twice per day on working days and once per day on weekends and holidays.
Symptoms: A clinical inspection was performed on each animal at least three times on exposure days and once a day during pre-exposure and post exposure observation days.
Body weight: The animals were weighed prior to the pre-exposure period, at the start of the exposure period (day 0) and twice weekly thereafter until one day prior to gross necropsy.
Clinical Pathology:
Blood was taken from the retrobulbar venous plexus in the morning from fasted animals using isoflurane as anesthesia. The blood sampling procedure and the subsequent analysis of the blood samples was carried out in a randomized sequence. The list of randomization instructions are compiled with a computer using a random number generator. The following parameters of the animals were examined. Hematology: Leukocytes, Erythrocytes, Hemoglobin, Hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelets, differential blood count, reticulocytes, preparation of blood smears.

Sacrifice and pathology:

Pathology:
Necropsy: The animals were sacrificed under pentobarbitone anesthesia by exsanguination from the abdominal aorta and vena cava. The animals were necropsied and assessed by gross pathology. Animals which die intercurrently or were killed in a moribund state were necropsied as soon as possible after their death and assessed by gross pathology.
Organ weights:
The following weights were determined in all animals sacrificed on schedule: anesthetized animals, adrenal glands, brain, heart, kidneys, liver, lungs, spleen, testes, thymus.
Organ / Tissue fixation:
The following organs or tissues were fixed in 4% buffered formaldehyde or modified Davidson’s solution: all gross lesions, adrenal glands, brain with olfactory bulb, bone marrow (femur), esophagus, eyes with optic nerve, heart, kidneys, larynx/pharynx, liver, lungs, lymph nodes (tracheobronchial and mediastinal lymph nodes), nose (nasal cavity), ovaries, seminal vesicle, spinal cord (cervical, thoracic and lumbar cords), stomach (forestomach and glandular stomach), spleen, testes (modified Davidson’s solution), thyroid glands, thymus, trachea, urinary bladder, uterus.
From the liver, each one slices of the Lobus dexter medialis and the Lobus sinister lateralis were fixed in Carnoy’s solution and embedded in paraplast. The testes were fixed in modified Davidson’s solution.
The liver and testes of animals that die or will have to be sacrificed intercurrently will be fixed in 4% buffered formaldehyde solution.
Histopathology
All gross lesions, nasal cavity, larrynx, trachea, lungs, lymph nodes, adrenal cortex ,adrenal medulla, bone marrow (femur), brain, esphagus, heart, kidneys, liver, lvaries, ovaries, seminal vesicles, spinal cord, spleen, stomach, testes, thymus, thyroid glands, uterus

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

no effects observed

Water consumption and compound intake (if drinking water study):

no effects observed

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

degeneration/regeneration of the olfactory epithelia at all levels, as well as loss of mucous cells

Histopathological findings: neoplastic:

no effects observed

Other effects:

no effects observed

Details on results:

The mean measured concentration was 18 ppm. In the nasal cavity degeneration/regeneration of the olfactory epithelia was observed at all levels, as well as loss of mucous cells. All other organs were free of any morphological changes.

Effect levels

Remarks on result:

other: nasal cavity degeneration/regeneration of the olfactory epithelia was observed at all levels, as well as loss of mucous cells

Applicant's summary and conclusion

Executive summary:

Five male and five female Wistar rats were whole-body exposed to vapor of 5-methyl-3-vinyl-oxazolidin-2-on for 6 hours a day on 5 days per week for 14 days (10 exposures). Due to low vapor pressure of the test substance, only the vapor saturation concentration was tested. A concurrent control group was exposed to clean air. Clinical inspection for any signs of toxicity was performed three times on exposure days and once daily on exposure-free days. Body weights were determined twice daily, hematology was performed at the end of the exposure period. The whole panel of organs and tissues listed in OECD test guideline 412 underwent histotechnical processing and were examined subsequently by light microscopy. The only effect observed was respiratory irritation in the nasal cavity. All other organs were free of any morphological changes.