Registration Dossier

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:
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:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
The relative humidity reached maximum value of 71 %
Qualifier:
according to
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

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:
male/female
Details on test animals 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:
There were no clinical signs of reaction to treatment.
Body weight:
All rats gained weight during the first and second weeks of the study except for one female which showed no change in body weight during the first week.
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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
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.