Dimethyl carbonate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 January 1992 - 07 February 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted in compliance with GLP, and although no specific test guideline was quoted in the method, a review of the methodology used revealed that the method used was essentially consistent with modern guideline tests, such as OECD TG 402, and so the data may be considered reliable.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

No specific test guideline was followed, but the methodology empolyed during the study was broadly consistent with a limit test as described in OECD TG 402. The test material was applied to the shaved but not abraded skin of five male and five female rabbits at 2000 mg/kg for a period of 24 hours. The test animals were then observed for 14 days after exposure.

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

Test material information

Constituent 1

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: Stable under the storage conditions.
- Storage condition of test material: Room temperature (approximately 22°C).
- Other:

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Johnson Rabbit Ranch, Wilkinson, IN
- Age at study initiation: Approximately 4 - 6 months of age (2-4 months on arrival at the laboratory, followed by a 10-week quarantine period).
- Weight at study initiation: 2.88 - 3.56 kg
- Fasting period before study: None recorded.
- Housing: The rabbits were housed individually in stainless steel cages measuring 61.0 x 45.5 x 41.0 cm. Polyzorb cage liners were placed in the pan below the stainless steel mesh floor of each animal cage.
- Diet (e.g. ad libitum): Each rabbit was provided approximately 150g Purina Lab Rabbit Chow HF #5326 daily.
- Water (e.g. ad libitum):Reverse-osmosis purified water was provided ad libitum.
- Acclimation period: Rabbits were held in quarantine for 10 weeks and examined to ensure their health and suitability as test subjects.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Average - 23°C.
- Humidity (%): Average - 38%.
- Air changes (per hr): Not reported.
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light / 12 hours dark.


IN-LIFE DATES: From: 23 January 1992 To: 07 February 1992

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 240 cm^2
- Type of wrap if used: Exposure site was covered by a surgical dressing, covered by plastic film then secured with a lint-free cloth and an elastic adhesive bandage.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): The application sites were rinsed with Amoco white mineral oil and towel dried.
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 g test substance per kg bodyweight.
- Constant volume or concentration used: Test substance was applied neat, therefore concentration was constant.

Duration of exposure:

24 Hours

Doses:

Single dose level, 2 g/kg

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All test rabbits were observed at frequent intervals after dosing and at least once per day for 14 days after removal of the wrappings. All animals were weighed immediately prior to dosing, once week after test substance application, and at the termination of the study.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No animals died during the study

Mortality:

No deaths occurred during the study.

Clinical signs:

other: Dermal irritation (i.e. edema and / or erythema) was observed within the application site of all rabbits following removal of the wrappings. However, signs of dermal irritation were no longer seen in an rabbit five days after unwrapping and all animals a

Gross pathology:

Gross necropsy findings were within normal limits in eight rabbits. Two males had multiple red foci on their lungs, 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 acute median lethal dermal dose (LD50) for Dimethyl Carbonate was estimated to be greater than 2 g/kg of body weight.