Dimethyl succinate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelman GmbH
- Age at study initiation: 8 weeks
- Weight at study initiation: 18.2 - 21.5 g
- Housing: Individually in Makrolon type II cages
- Diet (e.g. ad libitum): Altromen 1324forte, ad-libitum
- Water (e.g. ad libitum): Tap water, ad-libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.0deg C average
- Humidity (%): 46.1% average
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hpours dark

IN-LIFE DATES: From: 2004-04-19 To: 2004-04-27

Vehicle:

dimethylformamide

Concentration:

Low dose: 25% (v/v)
Mid dose 50% (v/v)
High dose: 100% (undiluted)

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS:
- Irritation: Minor increase in ear thickness, within the normal range

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA pooled lymph node method
- Criteria used to consider a positive response: 3 fold increase in stimulation index

TREATMENT PREPARATION AND ADMINISTRATION:
The substance was used undiluted or dissolved in dimethylformamide and administered to 3 groups of 5 female CBA/Ca mice. Administration was epicutaneous to the dorsal surface of both ears, once a day on 3 consecutive days. The volume administered was 25 μL per ear.

Two groups with 5 animals each served as positive and negative controls. Both control substances were administered under the same conditions as the test substance. The following solutions served as control substances:
- Positive control: 25% (v/v) solution of hexyl cinnamic aldehyde in acetone:olive oil (4:1, v/v)
- Negative control: Dimethylformamide

Five days after the first topical application, 3H-thymidine was intravenously administered to all mice via the tail vein. Approximately 5 hours later all animals were sacrificed, the draining auricular lymph nodes were excised, pooled for each group, and single cell suspensions were prepared. Incorporation of 3H-methyl thymidine into the cells was determined by liquid scintillation counter and compared with the negative controls.

The stimulation index (SI) was calculated as the ratio of the disintegrations per minute (dpm) of the dosed groups or of the positive control group relative to the dpm of the negative control group.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Positive control results:

SI - 25.4 (Positive)

Parameter:

SI

Value:

0.9

Test group / Remarks:

Low dose - 25%

Parameter:

SI

Value:

0.9

Test group / Remarks:

Mid dose - 50%

Parameter:

SI

Value:

0.7

Test group / Remarks:

High dose - 100%

Parameter:

SI

Value:

25.4

Test group / Remarks:

Positive control - 25%

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance does not act as a skin sensitiser

Executive summary:

A Local Lymph Node Assay has been performed to evaluate potential dermal sensitization using mthods described in OECD Test Guideline No. 429. Dimethyl succinate does not act as a skin sensitiser

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The substance has been investigated in the mouse using the Local Lymph Node Assay.

The assessment is based on a single, critical, study for the endpoint.

Justification for classification or non-classification

Non classification is justified based on the lack of evidence for dermal sensitisation using an accepted test method