Registration Dossier

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:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
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

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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.
Body weight:
All rats achieved body weight gains during the first and second weeks of the study.
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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
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.