Bis(2-ethylhexyl) succinate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 November 2012 to 13 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:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class 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:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 167 - 179 g (on day of dosing)
- Fasting period before study: animals were fasted from the evening of the day prior to dosing (day -1) until approximately 3 hours after dosing
- Housing: animimals were housed in groups up to 5 during the acclimation period and in groups of three from the day prior to dosing. Cages conformed to the Code of Practice for the Housing and Care of Animals Used in Scientific Procedures' (Home Ofice, London, 1989)
- Diet: ad libitum
- Water: mains water, ad libitum
- Acclimation period: 7 - 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 32 - 71 %
- Air changes (per hr): 15 - 20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

TEST MATERIAL FORMULATION
The test material was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.
Individual doses were calculated using the fasted body weights of the rats on the morning of dosing and the specific gravity of the neat test material.

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 females per treatment group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: animals were observed for clinical signs of reaction to treatment 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 once daily thereafter.
- Frequency of weighing: animals were weighed on the day prior to dosing and on days 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.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None of the animals died during the study.

Clinical signs:

other: Clinical signs were confined to decreased activity and hunched posture in three animals two hours after dosing. These signs persisted in two animals three hours after dosing.

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1: Individual Body Weights

Animal number	Body weight (g)
	day -1	day 1	day 4	day 8	day15
184	187	172	187	189	197
185	188	179	193	198	200
186	174	168	181	186	192
187	182	174	182	190	203
188	174	167	173	181	191
189	174	167	173	180	190

Table 2: Clinical Signs Following Treatment

Animals number	Clinical sign	Sign noted after dosing on day 1 (hours):			Sign noted on day 2 - 15
		1	2	3
187	decrease activity		X	X
	hunched posture		X	X
188	decrease activity		X	X
	hunched posture		X	X
189	decrease activity		X
	hunched posture		X

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study the acute oral LD50 of the test material was determined to be in excess of 2000 mg/kg bw.

Executive summary:

The acute oral toxicity of the test material was determined in a GLP study which was conducted in line with standardised guidelines OECD 423 and EU Method B.1 tris. During the study, two groups of three female rats were dosed test material, by gavage, at a dose level of 2000 mg/kg. Following administration, animals were observed for mortality and clinical signs, and body weights were recorded, over a period of 14 days. All animals were sacrificed on day 15 and underwent a full necropsy. None of the animals died during the study and clinical signs were confined to decreased activity and hunched posture in three animals two hours after dosing. These signs persisted in two animals three hours after dosing. All rats achieved body weight gains during the first and second weeks of the study and no abnormalities were noted at necropsy. Under the conditions of the study the acute oral LD50 of the test material was determined to be in excess of 2000 mg/kg bw.