Dimethyl sebacate

Endpoint summary

Description of key information

Dimethyl sebacate was found to be of low toxicity in an acute and dermal toxicity tests performed according to OECD 401 and OECD 402 guidelines, 
respectively.

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

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

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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

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

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

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.

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

 

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

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

Study period:

23 October 2012 to DATE

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Fully GLP compliant and in accordance with current guidelines

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester
- Age at study initiation: 9 to 11 weeks
- Weight at study initiation: 279 to 312 g (males) and 179 to 206 g (females)
- Housing: cages that conformed to the 'Code of Practice for the Housing and Care of Animals Used in Scientific Procedures' (Home Office, London, 1989)
- 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 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 32 to 66%
- 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: 20 November 2012 To: 12 December 2012

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsum
- % coverage: 10%
- Type of wrap if used: A dense gauze patch held in place with elasticated; open weave adhesive compression bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dermal test site of each rat was lightly brushed clean of any solid residues and swabbed with water-moistened cotton wool
- Time after start of exposure: 24 Hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 mL/kg
- Concentration (if solution): Not Applicable
- Constant volume or concentration used: yes
- For solids, paste formed: Not applicable

Duration of exposure:

15 Days

Doses:

One dose at 2000 mg/kg

No. of animals per sex per dose:

Five male and five female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: observations were undertaken 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. Rats were weighed on Day -1 (day before dosing) and on Days 1, 4, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Not applicable

Preliminary study:

No compound related mortality occurred in the preliminary test.

Sex:

male/female

Dose descriptor:

other: Discriminating dose

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: There were no clinical signs of reaction to treatment.

Gross pathology:

No macroscopic changes were noted at necropsy.

Table 1 Mortality data

Dose level (mg/kg)	Mortality ratio
	Male	Female
2000	0/5	0/5

 

Table 2 Clinical signs following treatment

Dose level: 2000 mg/kg

Clinical sign	Animal number and sex
	174M	175M	176M	177M	178M
No observations	ü	ü	ü	ü	ü

 

Clinical sign	Animal number and sex
	179F	180F	181F	182F	183F
No observations	ü	ü	ü	ü	ü

 

Key:

ü            No clinical signs seen throughout the observation period

 

Table 3 Dermal reactions

Dose level: 2000 mg/kg

Day	Dermal reaction	Animal number and sex
		174M	175M	176M	177M	178M
2	Erythema Oedema Other	0 0 -	0 0 -	0 0 -	0 0 -	0 0 -
3	Erythema Oedema Other	0 0 -	0 0 -	0 0 -	0 0 -	0 0 -
4	Erythema Oedema Other	0 0 -	0 0 -	0 0 -	0 0 -	0 0 -
5 to 15	Erythema Oedema Other	0 0 -	0 0 -	0 0 -	0 0 -	0 0 -

 

Day	Dermal reaction	Animal number and sex
		179F	180F	181F	182F	183F
2	Erythema Oedema Other	0 0 -	0 0 -	0 0 -	0 0 -	0 0 -
3	Erythema Oedema Other	0 0 -	0 0 -	0 0 -	0 0 -	0 0 -
4	Erythema Oedema Other	0 0 -	0 0 -	0 0 -	0 0 -	0 0 -
5 to 15	Erythema Oedema Other	0 0 -	0 0 -	0 0 -	0 0 -	0 0 -

 

Key:

-              No other dermal changes apparent

 

Table 4 Individual body weights and weekly increments

Dose level (mg/kg)	Animal number and sex	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	174M	276	287	282	290	322	3	32
	175M	313	310	316	330	343	20	13
	176M	299	299	305	318	333	19	15
	177M	277	279	284	290	309	11	19
	178M	312	312	319	330	353	18	23
2000	179F	177	180	175	178	195	-2	17
	180F	187	179	182	197	204	18	7
	181F	209	206	211	220	227	14	7
	182F	190	194	199	199	204	5	5
	183F	194	192	197	194	194	2	0

 

A minus symbol [-] indicates a body weight loss

 

Table 5 Necropsy findings

Dose level: 2000 mg/kg

Animal number and sex	Time and manner of death (Day)	Necropsy comments
174M	15T	No macroscopic changes
175M	15T	No macroscopic changes
176M	15T	No macroscopic changes
177M	15T	No macroscopic changes
178M	15T	No macroscopic changes
179F	15T	No macroscopic changes
180F	15T	No macroscopic changes
181F	15T	No macroscopic changes
182F	15T	No macroscopic changes
183F	15T	No macroscopic changes

 

T            Animal killed by isofluorane anaesthesia followed by exsanguination at completion of observation period

 

Interpretation of results:

other: No significant acute toxicity

Remarks:

Criteria used for interpretation of results: OECD GHS

Conclusions:

The acute median lethal dermal dose of Dimethyl Sebacate to rats was found to exceed 2000 mg/kg.
The test material was considered to have no significant acute toxic risk in respect of its acute dermal 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 determine the acute dermal toxicity of the test article, Dimethyl Sebacate following a single (24 hour) semi-occluded topical application to the rat. The test article was applied as an undiluted liquid to the clipped dorsum of a group of five male and five female rats on Day 1. Each rat received a single topical application at a dose level of 2000 mg/kg. The treated areas of dorsum were covered by a semi-occlusive dressing for 24 hours. All animals were killed on Day 15 and subsequently underwent a full necropsy. There were no deaths, no clinical signs of reaction to treatment and no overt dermal changes were noted at the test sites. All animals showed gains in body weight over the study period. No macroscopic changes were apparent at necropsy. The acute median lethal dermal dose of Dimethyl Sebacate to rats was found to exceed 2000 mg/kg. The test material was considered to have no significant acute toxic risk in respect of its acute dermal toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Acute oral toxicity sudy (Dreher, 2013)

This GLP study performed according to OECD guideline 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).

Acute dermal toxicity study (Dreher, 2013)

This GLP study performed according to OECD guideline 402 was conducted to determine the acute dermal toxicity of the test article, Dimethyl Sebacate following a single (24 hour) semi-occluded topical application to the rat. The test article was applied as an undiluted liquid to the clipped dorsum of a group of five male and five female rats on Day 1. Each rat received a single topical application at a dose level of 2000 mg/kg. The treated areas of dorsum were covered by a semi-occlusive dressing for 24 hours. All animals were killed on Day 15 and subsequently underwent a full necropsy. There were no deaths, no clinical signs of reaction to treatment and no overt dermal changes were noted at the test sites. All animals showed gains in body weight over the study period. No macroscopic changes were apparent at necropsy. The acute median lethal dermal dose of Dimethyl Sebacate to rats was found to exceed 2000 mg/kg. The test material was considered to have no significant acute toxic risk in respect of its acute dermal toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Justification for selection of acute toxicity – oral endpoint
The study was GLP and performed according to OECD guideline. No mortality or severe clinical signs were recorded.

Justification for selection of acute toxicity – dermal endpoint
The study was fully compliant and performed accroding to OECD guideline. There were no mortality or severse clinical signs.

Justification for classification or non-classification

No classification is warranted for oral and dermal acute toxicity under EU Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008.