Disodium sebacate

Endpoint summary

Description of key information

The oral LD50 was ≥ 5000 mg/kg in rats. The dermal LD50 of a structurally related compound was ≥ 2000 mg/kg.

 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 6-7 weeks.
- Weight at study initiation: ♂ 168 g, ♀ 146 g
- Housing: Animals were caged separated
- Fasting period before study: 18 h
- Diet: ad libitum, commercial pelleted diet (Oakes Special Diet with added Vit. E)
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ±2
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 5000 mg/kg
- Amount of vehicle: 25% (w/v) solution, 20 mL/kg

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical symptoms, gross pathology

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No substance related mortality was seen.

Clinical signs:

other: No substance related clinical effects were seen.

Gross pathology:

No pathological substance related changes were observed.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Klimisch code 2

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

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

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Italia S.p.A.
- Age at study initiation: not more than three months
- Weight at study initiation: ♂ 290 - 350 g; ♀ 247-286 g
- Housing: 5 animal per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ±2
- Humidity (%): 55 ±10
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 6x5 cm
- % coverage: 10 %
- Type of wrap if used: hypoallergenic non-irritaing tape

REMOVAL OF TEST SUBSTANCE
- Washing: yes, with water
- Time after start of exposure: 24 h

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 30 min, 2, 4, and 6 hours an the first day after the administration, twice a day up to termination
- Other examinations performed: clinical signs, body weight, histopathology, gross pathology

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No mortality occurred.

Clinical signs:

other: No general or local clinical abnormalities were seen in any animal.

Gross pathology:

No apprecible changes were evident in the treated animals of either sex at the autopsy carried out at the end of the observation period.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch code: 1

Additional information

Acute Oral Toxicity

In an acute oral toxicity study, a group of five male and five female Sprague Dawley rats were given a single oral dose of disodium sebacate at a discriminating dose of 5000 mg/kg bw. An observation period of 14 days followed administration. There were no treatment related clinical signs, necropsy findings or changes in body weight. The LD50 was considered to be greater than 5000 mg/kg bw. Similar findings were reported by Greco et al in both rats ands rabbits.

Acute Dermal Toxicity

In a GLP-compliant acute dermal toxicity study following OECD guidleine 402, groups of adult Sprague-Daley rats (5/sex) were dermally exposed to sebacic acid for 24 hours to 10 % (6 x 5 cm) skin surface at the dose of 2000 mg/kg bw. Animals then were observed for 14 days. There were no treatment related clinical signs, necropsy findings or changes in body weight. The LD50 was considered to be greater than 2000 mg/kg bw.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. Discriminating doses for acute oral (> 5000 mg/kg bw) and dermal (> 2000 mg/kg bw) toxicity were determined. As a result the substance is not considered to be classified for acute oral and dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the ninth time in Regulation (EC) No. 2016/1179.