4,4-dimethyloxazolidine

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1973

Report date:

1973

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: Acute Inhalation Toxicity of P-1585 (Oxazolodine-A) in male albino rats
- Short description of test conditions: The Acute Inhalation Toxicity of P-1585 was measured through exposure of the test substance as a mist for one hour. The rats were observed during the exposure duration and a period of 14 days. The rats were then necropsied.
- Parameters analysed / observed: pharmacodynamic and toxic signs during and after exposure period for 14 days; gross necropsy after 14 days or if the animal died during the observation period

GLP compliance:

not specified

Test type:

traditional method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4,4-dimethyloxazolidine

EC Number:

257-048-2

EC Name:

4,4-dimethyloxazolidine

Cas Number:

51200-87-4

Molecular formula:

C5H11NO

IUPAC Name:

4,4-dimethyl-1,3-oxazolidine

Test material form:

liquid

Specific details on test material used for the study:

- Name: P-1585 / Oxazolidine A 87.4%
- Source and lot/batch No.of test material: Commercial Solvents Corporation, Terre Haute, Indiana, lot 575916JH
- Purity: 87.4%

Test animals

Species:

rat

Strain:

other:

Remarks:

Spartan Strain

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 205 to 250 g
- Housing: metal cages
- Diet: Purina Laboratory Chew ad libitum
- Water: ad libitum


Temperature and humudity controlled quarters.

Administration / exposure

Route of administration:

inhalation: mist

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: sealed glass chamber
- Exposure chamber volume: 59.1 l
- Method of holding animals in test chamber: none, rats were separted into 4 units of 2 or 3 rats each
- Rate of air: 0.382 ml/min
- Method: Controlled by a Harvard Dual Infusion/Withdrawal Pump with a 50 cc syringe. Dried and filterted air was passed through the mechanism and directly into the exposure chamber. Airflow was regulated by means a flowmeter.
- Temperature, humidity, pressure in air chamber: not specified

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

1 h

Concentrations:

Calculated atmospheric concentrations: 3.125, 6.5, 12.5, 25 and 50 mg/l

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not specified
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

11.66 mg/L air

Based on:

test mat.

95% CL:

>= 9.3 - <= 14.63

Exp. duration:

1 h

Mortality:

None of the rats at atmospheric concentrations of 3.125 and 6.25 mg/l died during the exposure and the subsequent 14 day observation period.
Six of 10 rats at the 12.5 mg/l level died within 2 days of the observation period.
All rats receiving the test compound at concentrations of 25 and 50 mg/l died within 3 days after the exposure period.

Clinical signs:

other: Signs seen during the exposure period: 3.125 mg/l nasal discharge, eye squint, marked dyspnea (gasping), salivation, lacrimation, erythema, decreased respiratory rates and decreased motor activity. 6.25 mg/l: additionally ocular and nasal porphyrin disc

Body weight:

All surviving rats at the 3.125 and 6.25 mg/l exposures exhibited normal body weight gains. Rats surviving the 12.5 mg/l concentration exhibited body weight gains, however, the gains noted were considered less then the normal gains exhibited by untreated rats of this age and strain in this laboratory.

Gross pathology:

In rats dying at 25 & 50 mg/kg necropsy findings in most rats included bloody nasal discharge, moderate to severe lung hemorrhage, mode to severe congestion of the liver and corneal opacity and thickening (probalby edema). At 12.5 mg/kg findings in most rats were limited to liver and lung congestion. One rat at this level had hemorrhage with bloddy nasal discharge.

Any other information on results incl. tables

3.125 mg/l:

Signs seen during the exposure period included nasal discharge, eye squint, marked dyspnea (gasping), salivation, lacrimation, erythema, decreased respiratory rates and decreased motor activity. At 24 hours all rats were normal with the exception that corneal opacity, sweling of the conjunctival tissue and corneals lesions were observed. These signs of ocular irritation were noted throughout the 14 day observation period.

6.25 mg/l:

Signs seen during the exposure period were essentially those observed above at the 3.125 mg/l concentration. In addition ocular and nasal porphyrin discharge were observed. At 24 hours nasal discharge, gasping and nasal porphyrin discharge were observed as were corneal opacity and respiratory congestion. At 6 days corneal opacity and swelling of the conjunctival tissues was observed. These signs of ocular irritation continued in evidence for the duration of the observation period.

12.5 mg/l:

In addition to these signs noted above, ataxia was also observed at this concentration during the exposure. At 24 hours nasal discharge, prostration, nasal porphyrin discharge, blanching, decreased respiratory rates, ataxia and decreased motor activity were noted as was intermittent body jerking and respiratory congestion. One rat was found dead at 24 hours. At 48 hours dyspnea, decreased respiratory rates, respiratory congestion, corneal opacity, blanching and bloated abdomen were noted. Five rats were found dead at 48 hours. From 3 to 9 days respiratory congestion, and corneal opacity remained in evidence and during the 3rd, 4th and 5th days blanching was also observed. From the 10th to 14th day respiratory congestion and corneal opacity, continued in evidence. Also observed at this time was corneal balging, lesions on the corneal surface and swelling of the conjunctial tissue.

25 and 50 mg/l:

Signs noted at each of these levels during the exposure period were essentially similar to those observed at the 12.5 mg/l concentration. In addition, blood and foam emitted from the nose, intermittent body jerking, respiratory congestion and blanching were observed at both atmospheric concentrations. At 24 hours signs observed at each of these levels included marked dyspnea (gasping), nasal porphyrin discharge, blanching, decreased respiratory rates, ataxis, decreased motor activity, respiratory congestion, myasthenia and corneal opacity. In addition nasal discharge, foam emitted from the nose and ocular porphyrin discharge also were observed at the 50 mg/l concentration. Three rats were found dead at the 25 mg/l concentration and 2 at the 50 mg/ l concentration at 24 hours. At 48 hours, 6 rats were dead at the 25 mg/l concentration and 7 ras at the 50 mg/ l level. The one surviving rat in each group exhibited signs similar to those noted at 24 hours. The surviving rat in each group was found dead at 3 days.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Based upon the results obtained, the acute inhalation toxicity (LC50) of P-1585 Oxazolidine- A, in the male albino rat after 1h exposure was found to be 11.66 mg/l with confidence limits from 9.3 to 14.63 mg/l.
The calculated LC50 for male rat exposed during 4 h is 11.6 mg/l /4= 2.91 mg/l.

Executive summary:

Based upon the results obtained, the acute inhalation toxicity (LC50) of P-1585 Oxazolidine- A, in the male albino rat after 1h exposure was found to be 11.66 mg/l with confidence limits from 9.3 to 14.63 mg/l.

The calculated LC50 for male rat exposed during 4 h is 11.6 mg/l /4= 2.91 mg/l.