Diisopropyl succinate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 April 1998 to 17 September 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Diisopropyl succinate

EC Number:

213-110-0

EC Name:

Diisopropyl succinate

Cas Number:

924-88-9

Molecular formula:

C10H18O4

IUPAC Name:

diisopropyl succinate

Details on test material:

Name: "BERNSTEINSÄUREDIISOPROPYLESTER".
Chemical name: Di-iso-propylsuccinate.
Trade name: Diisopropylsuccinat (DIPS).
CAS No.: 924-88-9.
EINECS No.: 2131100.
Batch No.: EMBS 302.
Purity: 99 % (min.).
Solubility in water: 25 g/l (at 20 °C).
Density: 0.9847 g/cm3 (at 20 °C).
Vapour pressure: 10 hPa (at 20 °C).
Boiling point: 247 °C.
Flash-point: 105 °C.
Ignition temperature: 430 °C.
Appearance: Colourless liquid.
Odour: Perceptible.
Conditions of storage: In the refrigerator, in the dark.
Stability at conditions of storage: 12 months.
Stability at ambient temperature: 6 months.
Date of expiry: 31 December 1998.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Species, strain: Rats, Sprague Dawley, Him:OFA, SPF.
Supplier: Forschungsinstitut für Versuchstierzucht, A-2325 Himberg.
Number of animals and sex: 5 males and 5 females.
Age: Approximately 8 weeks (males) and 12 weeks (females) at the time of administration.

Hygiene: Improved hygienic conditions.
Room number: EH1-18.
Room temperature: Average of 22 °C.
Relative humidity: Average of 55 %.
Air exchange: 12 per hour.
Light: Artificial light from 6 a.m. to 6 p.m.
Cages: Single caging in Makrolon cages type III (39 cm x 23 cm x 15 cm). Wire mesh lids. Sanitation of cages once a week.
Bedding material: Aspen wood chips, type "4 HV" (Finn Tapvei Oy, SF-73620 Kortteinen), autoclaved. Bedding material was changed weekly.
Feed: Altromin 1314 forte, gamma irradiated with 25 kGy 60Co, ad libitum (Producer: Altromin GmbH, D-32791 Lage). Exception: Feed was withdrawn the evening before administration of the test substance and was offered again about three hours afterwards. Random samples of the feed are analysed for contaminants by Altromin.
Water: Tap water, offered in Makrolon bottles with stainless steel canules, ad libitum.
Identification: Labelling with felt-tipped pen on the tail and on the cage.
Acclimatisation: 7 days.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Test substance preparations:
Corn oil was used for the suspension of the test substance. The suspension was prepared freshly before administration and was given within 20 minutes afterwards.

Route of administration and administration technique:
A peroral administration was performed once in the morning by stomach intubation using a metal gavage. The dose volume was 5 ml per kg body weight. The individual dose volumes were calculated using the body weights determined at the day of the administration.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Observations in life:
Observations were performed within the periods 0 - 0.5, 0.5 - 1, 1 - 2, 2 - 4 and 4 - 6 hours after administration (p.a.) of the test substance and then at least once a day for a total of 2 weeks. Observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions.

Body weight and body weight gain:
Body weight was determined
before administration.
7 days p.a.
14 days p.a.
Body weight gain was calculated for each week of the study, i.e. between
0 and 7 d p.a.
7 and 14 d p.a.

Necropsy:
All animals were killed by CO2 14 days p.a. and subjected to a necropsy including a gross pathological examination.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

All animals survived until the scheduled termination of the study.

Clinical signs:

other: All animals were affected in any way. The findings were: Central nervous effetcs: Sedation, eyelid closure, tremor and/or disturbed locomotion in one male and three females immediately after administration of the test substance or up to one day thereaft

Gross pathology:

All animals were normal at the post mortem examination.

Other findings:

Sex differences:
Female animals were considered to be slightly more susceptible to effects of the test substance at a dose of 2000 mg per kg body weight than male animals.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance caused transient central nervous effects and signs of reduced well-being and of pain at the dose of 2000 mg/kg body weight. No mortality occurred.
The LD50,oral of "BERNSTEINSÄUREDIISOPROPYLESTER" is higher than 2000 mg/kg body weight in rats.

Executive summary:

It was the aim of the study to investigate acute toxic effects of the test substance after a single peroral administration.

Methods

The guidelines EC 92/69, method B.1., and OECD 401, 1987, were applied.

Administration

"BERNSTEINSÄUREDIISOPROPYLESTER", freshly suspended in corn oil, was administered once orally by stomach intubation to Him:OFA Sprague Dawley rats. The dose was 2000 mg per kg body weight. The dose volume was 5 ml per kg body weight.

Investigations

Body weight: before administration, 7 and 14 days after administration (p.a.).

Clinical observations: at least once per day.

Necropsy: 14 days p.a.

Results

Mortality

All animals survived until the scheduled termination of the study.

Body weights

Males and females: Mean body weights were inconspicuous. Body weight gains of the male animals were also inconspicuous. Females gained markedly less weight between Days 7 to 14 p.a. compared to Days 0 to 7 p.a.

Observations in life

All animals were affected in any way:

Sedation, eyelid closure, tremor and disturbed locomotion indicate central nervous effects of the test substance and were mainly observed in female animals. Hunched posture is interpreted as a sign of pain. Piloerection, chromodacryorrhoea and

soiling of the anogenital region are interpreted as signs of reduced well-being. The signs were observed mainly on the day of administration of the test substance and lasted in the affected animals until a maximum of 4 days p.a. All animals were normal at the end of the study.

Necropsy findings

All animals were normal at the post mortem examination.

Sex differences

Female animals were slightly more susceptible to effects of the test substance at a dose of 2000 mg per kg body weight than male animals.

Conclusion

The test substance caused transient central nervous effects and signs of reduced well-being and of pain at the dose of 2000 mg/kg body weight. No mortality occurred.

The LD50,oral of "BERNSTEINSÄUREDIISOPROPYLESTER" is higher than 2000 mg/kg body weight in rats.

According to Commission Directive 2001/59/EC the test substance does not require classification for acute oral toxicity.