Diethyl carbonate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data from Peer reviewed publication

Data source

Reference

Reference Type:

publication

Title:

ICCVAM Test Method Evaluation Report. The Reduced Murine Local Lymph Node Assay: An Alternative Test Method Using Fewer Animals to Assess the Allergic Contact Dermatitis Potential of Chemicals and Products

Author:

NIH

Year:

2009

Bibliographic source:

NIH Publication No. 09-6439. National Institutes of Health

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Principles of method if other than guideline:

The protocol for the reduced LLNA is identical to that of the traditional LLNA with one exception. In the traditional LLNA, three dose levels of each test substance are tested, while in the rLLNA only the highest dose level that does not induce systemic toxicity and/or excessive skin irritation is tested for skin sensitizing activity. The term “limit dose”, sometimes used to refer to the rLLNA, accurately depicts a modified LLNA that tests only the highest dose level that does not induce local irritation and/or systemic toxicity. The terms “cut-down” and “reduced” LLNA also accurately describe the reduction in the number of doses tested and emphasize the reduction in the number of animals used to perform the test.
The rLLNA measures lymphocyte proliferation after topical exposure to a potential skin sensitizing substance. The test substance is administered topically on three consecutive days to the ears of mice at a concentration that provides maximum solubility of the test substance without systemic toxicity and/or excessive local irritation. Two days after the final application of the test substance, 3H-thymidine or [125]I-iododeoxyuridine (in phosphate-buffered saline; 250 uL/mouse) is administered via the tail vein. Five hours later the draining auricular lymph nodes are excised, and a single-cell suspension from the lymph nodes of each animal is prepared for quantifying the incorporation of radioactivity, which correlates with lymph node cell proliferation. The incorporation of radioactive 3H-thymidine or [125]I-iododeoxyuridine for each mouse is expressed in disintegrations per minute (dpm). The SI is calculated as the ratio of the mean dpm/mouse for each treatment group against the mean dpm/mouse for the vehicle control group. The threshold for a positive response is an SI of >= 3.

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

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

IUPAC Name:

dimethyl carbonate

Test material form:

other: liquid

Details on test material:

not further specified

In vivo test system

Test animals

Species:

mouse

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

not further specified

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

0.5, 5 and 50%

No. of animals per dose:

no data

Details on study design:

The protocol for the reduced LLNA is identical to that of the traditional LLNA with one exception. In the traditional LLNA, three dose levels of each test substance are tested, while in the rLLNA only the highest dose level that does not induce systemic toxicity and/or excessive skin irritation is tested for skin sensitizing activity. The term “limit dose”, sometimes used to refer to the rLLNA, accurately depicts a modified LLNA that tests only the highest dose level that does not induce local irritation and/or systemic toxicity. The terms “cut-down” and “reduced” LLNA also accurately describe the reduction in the number of doses tested and emphasize the reduction in the number of animals used to perform the test.
The rLLNA measures lymphocyte proliferation after topical exposure to a potential skin sensitizing substance. The test substance is administered topically on three consecutive days to the ears of mice at a concentration that provides maximum solubility of the test substance without systemic toxicity and/or excessive local irritation. Two days after the final application of the test substance, 3H-thymidine or [125]I-iododeoxyuridine (in phosphate-buffered saline; 250 uL/mouse) is administered via the tail vein. Five hours later the draining auricular lymph nodes are excised, and a single-cell suspension from the lymph nodes of each animal is prepared for quantifying the incorporation of radioactivity, which correlates with lymph node cell proliferation. The incorporation of radioactive 3H-thymidine or [125]I-iododeoxyuridine for each mouse is expressed in disintegrations per minute (dpm). The SI is calculated as the ratio of the mean dpm/mouse for each treatment group against the mean dpm/mouse for the vehicle control group. The threshold for a positive response is an SI of >= 3.

Positive control substance(s):

not specified

Statistics:

Yes

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: The calculated stimulation indices were given with 0.64, 0.69 and 1.71

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: no details reported

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

Dimethyl carbonate was tested in a reduced LLNA (the protocol for the rLLNA is identical to that of the traditional LLNA with one exception, as only the highest dose level that does not induce systemic toxicity and/or excessive skin irritation is tested for skin sensitizing activity), where concentrations of 0.5, 5 and 50% have been tested. The calculated stimulation indices were given with 0.64, 0.69 and 1.71, i.e. the substance gave no indications for a skin sensitizing potential.

Executive summary:

Dimethyl carbonate was tested in a reduced LLNA (the protocol for the rLLNA is identical to that of the traditional LLNA with one exception, as only the highest dose level that does not induce systemic toxicity and/or excessive skin irritation is tested for skin sensitizing activity), where concentrations of 0.5, 5 and 50% have been tested. The calculated stimulation indices were given with 0.64, 0.69 and 1.71, i.e. the substance gave no indications for a skin sensitizing potential.