Bis(2-ethylhexyl) succinate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 December 2012 to 27 December 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

yes

Remarks:

The relative humidity reached maximum value of 71 %

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

The relative humidity reached maximum value of 71 %

Principles of method if other than guideline:

The relative humidity reached maximum value of 71 %, 1 % higher than the maximum recommended in the guidelines. This deviations was not considered not to have affected the integrity or outcome of the study.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2-ethylhexyl) succinate

EC Number:

220-836-1

EC Name:

Bis(2-ethylhexyl) succinate

Cas Number:

2915-57-3

Molecular formula:

C20H38O4

IUPAC Name:

1,4-bis(2-ethylhexyl) butanedioate

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Bis(2-ethylhexyl) Succinate
- Storage condition of test material: In a sealed container, at room temperature, in the dark

Test animals

Species:

rat

Strain:

other: HsdHan:WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8 - 10 weeks
- Weight at study initiation: 236 - 302 g (males); 173 - 202 g (females)
- Housing: in groups up to 5 by sex during acclimation and individually from the day prior to dosing. After completion of the day 3 observations animals allocated to the main study were returned to group housing. Cages conformed to the 'Code of Practice for the Housing and Care of Animals Used in Scientific Procedures' (Home Office, London, 1989)
- Diet: ad libitum
- Water: mains warer, ad libitum
- Acclimation period: 8 to 16 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 45 - 71 %
- Air changes (per hr): 15 - 20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
Hair from the dorsum was removed with electric clipper on the day before dosing. the dermal site was an area of at least 10 % of the total body surface. The test material was spread evenly across the dermal test site. A dense gauze patch was placed over the treated skin, held in places with and elasticated, open-weave, adhesive compression bandage. this was wrapped securely around the torso of the animal.

REMOVAL OF TEST SUBSTANCE
The dressing was removed approximately 24 hours after application. The dermal test site of each rat was lightly brushed clean of any solid residues and swabbed with water-moistened cotton wool before the animal was returned to the holding cage.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): individual dose volumes were calculated from the body weights of the rats on the morning of dosing (day 1), taking account of the specific gravity of the test material (0.914 g/mL). The dose volume applied to each animal was 2.19 mL/kg (dose level: 2000 mg/kg bw).

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 males and 5 females per group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: clinical signs were recorded immediately post-dose and approximately 15 and 30 minutes, and 1, 2, 3 and 4 hours post-dose on day 1, twice daily on days 2, 3 and 4 and daily thereafter.
- Frequency of weighing: animals were weighed on days -1, 1, 4, 8 and 15
Necropsy of survivors performed: yes. A full macroscopic examination was performed and all lesions recorded. The necropsy procedure included inspection of the external surfaces and orifices, all viscera and tissue within the abdominal, thoracic and cranial cavities, free-hand sectioning of the liver and kidneys and examination of representative sections of mucosal surfaces of the stomach, small and large intestines.
- Other examinations performed: dermal reactions. The condition of the dermal test site was recorded following removal of the dressing on day 2 and once daily thereafter. erythema and oedema were scored according to the Draize scale (Table 1).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mL/kg bw

Based on:

test mat.

Mortality:

None of the animals died during the study.

Clinical signs:

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

Gross pathology:

No macroscopic changes were noted at necropsy.

Other findings:

There were no dermal reactions.

Any other information on results incl. tables

Table 2: 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	194M	231	236	241	259	270	23	11
	195M	267	271	271	280	301	9	21
	196M	297	302	295	312	324	10	12
	197M	261	268	266	274	297	6	23
	198M	288	296	292	310	332	14	22
2000	203F	183	183	189	194	202	11	8
	204F	189	194	191	198	205	4	7
	205F	198	202	196	207	218	5	11
	206F	185	189	183	189	203	0	14
	207F	180	173	175	183	195	10	12

Table 3: Dermal Reactions - Males

Day	Dermal reaction	Animal number and sex
		194M	195M	196M	197M	198M
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 -

 

Dermal Reactions - Females

Day	Dermal reaction	Animal number and sex
		203F	204F	205F	206F	207F
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 -

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the test, the acute dermal median lethal dose of the test material was estimated to be in excess of 2000 mg/kg to male and female rats.

Executive summary:

The acute dermal toxicity of the test material was determined in a GLP study which was conducted in accordance with standardised guidelines OECD 402 and EU Method B.3. During the study five male and female rats received a single dermal application of 2000 mg/kg of the test material and were assessed daily for the following 14 days for any signs of systemic toxicity. None of the animals died and there were no signs of systemic toxicity. There were no dermal reactions and all animals gained weight during the study. There were no macroscopic abnormalities at examination post mortem. The acute dermal median lethal dose of the test material was estimated to be in excess of 2000 mg/kg to both male and female rats.