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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 January 1992 - 13 February 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted in accordance with GLP, and the methodology used is essentially compatible with modern testing guidelines such as OECD TG 403.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Principles of method if other than guideline:
Dimethyl Carbonate was administered as a vapor by a single inhalation exposure to a group of five male and five female Sprague-Dawley rats at a target concentration of 5.0 mg/L. Exposure time was 4 hours, and the animals were subsequently observed for a period of 14 days.
GLP compliance:
yes
Remarks:
The study report includes a GLP compliance statement signed by the study director, and a statement of Quality Assurance, although a certificate of GLP accreditation issued by an independent authority was not provided.
Test type:
fixed concentration procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Dimethyl carbonate
EC Number:
210-478-4
EC Name:
Dimethyl carbonate
Cas Number:
616-38-6
Molecular formula:
C3H6O3
IUPAC Name:
dimethyl carbonate
Details on test material:
- Name of test material (as cited in study report): Dimethyl Carbonate
- Physical state: clear colourless liquid
- Analytical purity: Not reported
- Lot/batch No.: LF-9135
- Expiration date of the lot/batch: Not reported
- Stability under test conditions: MSDS indicated that the test material was stable under the storage conditions used.
- Storage condition of test material: Initially stored at 22°C, later stored at refrigerated conditions (approximately 3°C) to minimise evaporative losses.
- Other:

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, Portage, MI.
- Age at study initiation: Approximately 7 weeks of age (6 weeks on arrival at the laboratory, followed by a one-week quarantine period).
- Weight at study initiation: 175 - 215 g
- Housing:The rats were housed individually in suspended stainless steel cages (15.8 x 15.5 x 17.0 cm); deotized animal cage boards were provided beneath the suspended cages.
- Diet (e.g. ad libitum): Ad libitum access to Purina Rodent Chow 5001.
- Water (e.g. ad libitum): Ad libitum access to reverse osmosis-purified water.
- Acclimation period:A quarantine period of approximately one week was conducted prior to commencement of the study.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C (average)
- Humidity (%): 35% (average)
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light followed by 12 hours darkness.


IN-LIFE DATES: From: 28 January 1992 To: 13 February 1992

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Glass and stainless steel cages
- Exposure chamber volume: 0.5 m^3
- Source and rate of air: Compressed air, 102 L/min.
- System of generating particulates/aerosols: Glass column packed with glass beads - test substance was delivered at a constant rate onto the middle of the column. Compressed air entered at the bottom of the glass bead column. The resultant vapour entered the chamber supply air duct and was carried to the top of the chamber. Neither the generator nor the test article was heated.
- Treatment of exhaust air: Chamber exhaust was passed through a HEPA and charcoal filter before being released to the outside environment.
- Temperature, humidity, pressure in air chamber: 26.1°C, 21% relative humidity. Pressure not reported.


TEST ATMOSPHERE
- Brief description of analytical method used: The test article vapor concentration was measured using a Wilks MIRAN IA-CVF infra-red (IR) spectrophotometer at a wavelength of 10.0 microns. The spectrophotometer was calibrated by preparing a calibration curve using a closed loop technique, wherein known quantities of test article were injected into the instrument and the instrument response was plotted versus test article concentration. The test atmosphere in the exposure chamber was sampled continuously during the exposure, readings were recorded periodically (i.e., approximate half hour intervals) and the concentration was calculated from the predetermined calibration curve.
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Periodic monitoring using an infra-red spectrophotometer.
Duration of exposure:
4 h
Concentrations:
Mean vapour concentration was 5.36 mg/L, minimum / maximum = 4.56 / 5.77 mg/L (analysed values).
No. of animals per sex per dose:
Five males and five females.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were weighed prior to exposure, one week later, and immediately prior to necropsy. The rats were observed immediately after removal from the chamber, approximately 0.5, 0.75, 1, 1.25, 2.25, and 3.25 hours after the exposure and at least once per day for the balance of the 14-day observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.36 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
None of the rats died during the study.
Clinical signs:
other: One males had redness around the nose for approximately one hour following exposure. Otherwise no adverse clinical signs were observed during the study.
Body weight:
All rats gained weight during the study.
Gross pathology:
Necropsy findings were within normal limits in seven rats. One male rat had external hemorrhagic lung foci; these foci were of a type and number (i.e., fewer than 10) commonly seen in control rats and were not considered treatment-related. One male and one female rats had distended bladders but the condition was not considered treatment-related.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of this study, the 4-hour acute inhalation median lethal concentration (LC50) of Dimethyl Carbonate in male and female rats is estimated to be greater than 5.36 mg/L.