Dimethyl sebacate

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

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

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
Receipt date: 11 October 2012
Storage: stored in a sealed container, at 15 to 25ºC, in the dark.

Test animals

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

Administration / exposure

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

Results and discussion

Preliminary study:

No compound related mortality occurred in the preliminary test.

Effect levels

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.

Any other information on results incl. tables

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

 

Applicant's summary and conclusion

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).