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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 January 1992 - 14 February 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to GLP and the methodology used was broadly consistent with modern test guidelines.

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 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
A group of five male and five female rats were dosed by oral gavage at 5 g/kg, observed for 14 days, then sacrificed and a gross necropsy performed.
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 dose 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: Sponsor confirmed that test material was stable at each storage condition, below.
- Storage condition of test material: Room temperature (approximately 22°C) from receipt on 17 January 1992, but moved to refrigerated storage (approximately 3°C) from 23 January 1992.
- 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 (Approximately 6 weeks of age on arrival at laboratory, then held in a quarantine for one week)
- Weight at study initiation: 182 - 222g (Non-fasted values)
- Fasting period before study: 18 hours prior to dosing
- Housing: Housed individually in stainless steel cages (24.0 x 17.8 x 17.6 cm) suspended over deotized animal cage boards.
- Diet (e.g. ad libitum): Purina Rodent Chow 5001 was provided ad libitum.
- Water (e.g. ad libitum): Reverse osmosis purified water was supplied as libitum.
- Acclimation period: One week (quarantine period to assess health and suitablility for the test)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C (Average)
- Humidity (%): 36% (Average)
- Air changes (per hr): Not reported.
- Photoperiod (hrs dark / hrs light): 12 Hours light / 12 hours dark.


IN-LIFE DATES: From: 31 January 1992 (Date of dosing) To: 14 February 1992

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: Not reported as dependent on animal weight. Doses were administered by weight but measured by volume, the density of the test material (1.071 g/mL) being used for the conversion.
Doses:
5g/kg (All animals)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were recorded frequently on the day of dosing, then daily for the remainder of the observation period. Rats were weighed prior to fasting, prior to dosing, and on days 7 and 14 of the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
None of the rats died during the study
Clinical signs:
Nine of the rats appeared sedated immediately after dosing, as evidenced by hypoactivity, ataxia and, in one rat, loss of the righting reflex. Seven rats still showed signs of ataxia the next morning; however, by the second day following dosing these signs had disappeared and the animals remained essentially normal for the duration of the study. Other minor clinical signs, mostly with very low incidence, included lacrimation, salivation, redness around the nose/eyes, discoloration around the mouth and of the paws, clear nasal discharge and hairloss under the chin.
Body weight:
All rats gained weight during the study.
Gross pathology:
Findings were within normal limits in all rats.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of this study, the acute median lethal oral dose (LD50) of Dimethyl Carbonate in male and females rats was estimated to be greater than 5 g/kg of bodyweight.