Dimethyl succinate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From February 25,2010 to March 16,2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl succinate

EC Number:

203-419-9

EC Name:

Dimethyl succinate

Cas Number:

106-65-0

Molecular formula:

C6H10O4

IUPAC Name:

dimethyl succinate

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot No.of test material: T14B208335
- Production date: 30 Nov 2008
- Expiration date of the lot/batch: 31 December 2010

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Italy S.r.l., 33049 San Pietro al Natisone (UD), Italy
- Age at study initiation: 6 to 8 weeks old
- Weight at study initiation: 176 to 200 grams
- Housing: Polycarbonate cages measuring 42.5x26.6x18 cm with stainless steel mesh lid and floor.
- No. of animals/cage: Individually caged (both during acclimatisation and study)
- Cage tray control: Daily inspected and changed as necessary (at least 3 times/week)
- Diet:4 RF 18 (Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI) Italy) , ad libitum throughout the study
- Water :drinking water supplied to each cage via a water bottle , ad libitum.
- Acclimation period: At least 5 days
- Veterinary health check: After arrival
- Choise of species:The Sprague Dawley SD rat was used, being the species and strain of choice because it is accepted by many regulatory authorities and there is ample experience and background data on this species and strain.
- Choice of the route: The route of administration is a potential route of exposure during manufacturing, handling or use of the substance.
- Room lighting: Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours
- Air changes : Approximately 15 to 25 air changes per hour
- Temperature range:22°C ± 2°C
- Relative humidity range: 55% ± 15%
Actual conditions were monitored, recorded and the records retained. No relevant deviations occurred.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Exposure time :24 hours
Washing procedure:After exposure, the adhesive bandage and gauze patch were removed. The treatment area was cleaned by gentle swabbing of the skin with cotton wool soaked with lukewarm water.

Duration of exposure:

24 hours

Doses:

single dose at level of 2000/mg/kg bw

No. of animals per sex per dose:

5 animals /sex/dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:Allocation (Day-1), Days 1, 8 and 15
- Necropsy of survivors performed: yes
- Clinical signs: controlled on the Day of dosing (on dosing, approximately 1, 2 and 4 hours after dosing). Daily thereafter (14 days).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred and no clinical signs were observed in male or female animals during the observation period.

Clinical signs:

other: No clinical signs were observed in male or female animals during the observation period.

Gross pathology:

No abnormalities were found at necropsy examination performed on all animals at termination of the study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

No mortality occurred following dosing and no signs of toxicity were observed.
These results indicate that the test item, Dimethyl Succinate (DMS), has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg.

Executive summary:

Acute dermal toxicity has been investigated according to OECD/EU test methods. No mortality occurred and no clinical signs were observed at a limit dose level of 2000 mg/kg, demonstrating the LD50 to be in excess of this value .