Dimethyl sebacate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 October 2012 to 05 April 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Fully GLP compliant and in accordance with current test guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl sebacate

EC Number:

203-431-4

EC Name:

Dimethyl sebacate

Cas Number:

106-79-6

Molecular formula:

C12H22O4

IUPAC Name:

1,10-dimethyl decanedioate

Test material form:

other: Solid to liquid (melting point 23°C)

Details on test material:

Name: Dimethyl Sebacate
CAS number: 106-79-6
Batch number: 120801
Purity: 99.08%
Expiry date: 31 August 2013
Date of receipt: 11 October 2012
Storage: stored in a sealed container, at room temperature in the dark.

Test animals

Species:

rat

Strain:

other: HsdHan:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester
- Age at study initiation: 8 to 9 weeks of age
- Weight at study initiation: 168 to 187g
- Fasting period before study: from the evening of the day prior to dosing (Day -1) until approximately 3 hours after dosing
- Housing: housed in groups of up to five during the acclimatisation period in cages that conform to the 'Code of Practice for the Housing and Care of Animals Used in Scientific Procedures' (Home Office, London, 1989). From the day prior to dosing (Day –1), the rats were housed in groups of three in similar cages.
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No 1, ad libitum
- Water (e.g. ad libitum): Mains water was provided, ad libitum
- Acclimation period: 7 to 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 45 to 65%
- Air changes (per hr): 15 to 20 air changes per hour.
- Photoperiod (hrs dark / hrs light): The rooms were illuminated by fluorescent strip-lights for twelve hours daily.

IN-LIFE DATES: From: 5 November 2012 To: 22 November 2012

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Not applicalbe
- Amount of vehicle (if gavage): Not applicalbe
- Justification for choice of vehicle: Not applicalbe
- Lot/batch no. (if required): Not applicable
- Purity: Not applicable

MAXIMUM DOSE VOLUME APPLIED: 2 mL/kg

DOSAGE PREPARATION (if unusual): The test article was warmed to approximately 30ºC until it was in liquid form and dosed without dilution. The liquid test article was shaken immediately prior to use to ensure homogeneity.

- Rationale for the selection of the starting dose: Since there were no data to indicate that deaths may occur at dose levels of less than 2000 mg/kg, the first dose level was 2000 mg/kg.

Doses:

A dose level of 2000 mg/kg with a specific gravity of 1.003 g/mL and a dose volume of 2 mL/kg

No. of animals per sex per dose:

3 animals per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Rats were weighed on Day -1 (day before dosing) and on Days 1, 4, 8 and 15. Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs were recorded immediately post dose, at approximately 15 and 30 minutes post dose, hourly between 1 and 4 hours post dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period.
- Necropsy of survivors performed: yes

Statistics:

Not required

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths.

Clinical signs:

other: No clinical signs were seen.

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1 Mortality data

Dose level (mg/kg)	Mortality ratio
2000	0/6

 

Table 2 Clinical signs following treatment

Dose level: 2000 mg/kg

Clinical sign		Animal number
		118		119		120		121		122		123
No observations		ü		ü		ü		ü		ü		ü

 

Key:

ü            No clinical signs seen throughout the observation period

 

Table 3 Individual body weights and weekly increments

Dose level (mg/kg)	Animal number	Body weight (g) at:					Increment (g)
		Day -1	Day 1	Day 4	Day 8	Day 15	Day 1 to 8	Day 8 to 15
2000	118	168	159	175	177	183	18	6
	119	176	163	178	182	190	19	8
	120	187	181	195	200	207	19	7
2000	121	177	169	180	189	185	20	-4
	122	173	163	176	184	191	21	7
	123	176	168	178	172	185	4	13

 

A minus symbol [-] indicates a body weight loss

 

Table 4 Necropsy findings

 

Dose level: 2000 mg/kg

Animal number	Time and manner of death (Day)	Necropsy comments
118	15T	No macroscopic changes
119	15T	No macroscopic changes
120	15T	No macroscopic changes
121	15T	No macroscopic changes
122	15T	No macroscopic changes
123	15T	No macroscopic changes

 

T            Animal killed by isofluoranean aesthesia followed by exsanguinations at completion of observation period

 

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The acute median lethal oral dose level of the test article, Dimethyl Sebacate, was found to exceed 2000 mg/kg.
The test material was considered to have no significant acute toxic risk in respect of its acute oral toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Executive summary:

This study was conducted to assess the acute toxicity of the test article, Dimethyl Sebacate, following a single oral administration to small groups of rats. The study design provides information for hazard assessment and classification and enables a chemical to be assigned to toxicity classes but severely restricts animal usage.

Groups of three female fasted rats were given the test article as a single dose on Day 1 by oral gavage at a dose level of 2000 mg/kg. All animals were killed on Day 15 and subsequently underwent a full necropsy.

There were no deaths and no clinical signs of reaction to treatment.

All rats achieved body weight gains over the study period.

No abnormalities were noted at necropsy.

The acute median lethal oral dose level of the test article, Dimethyl Sebacate, was found to exceed 2000 mg/kg.

The test material was considered to have no significant acute toxic risk in respect of its acute oral toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).