Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 May 2015 to 11 June 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP 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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Appearance: Slightly yellow powder with lumps
- Storage conditions of test material: At room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Wistar strain, Crl:WI (Han) (outbred, SPF-Quality)
- Age at study initiation: Young adult animals (approx. 12 weeks old)
- Weight at study initiation (mean on day 1): Males: 329 g; Females: 212 g. Body weight variation did not exceed ± 20 % of the sex mean
- Fasting period before study: No
- Housing: During acclimatisation, animals were group housed (cage height 18 cm). During the study, animals were individually housed in labelled cages (height 18 cm) containing sterilised sawdust as bedding material and paper as cage-enrichment.
- Diet: Free access to pelleted rodent diet
- Water: Free access to tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 to 24 °C
- Humidity: 40 to 70 % (relative)
- Air changes: at least 10 air changes/hour
- Photoperiod: 12-hour light/12-hour dark cycle

IN-LIFE PHASE
From: 28 May 2015
To: 11 June 2015

Administration / exposure

Type of coverage:
occlusive
Vehicle:
corn oil
Details on dermal exposure:
TEST SITE
- Area of exposure: One day before exposure (Day -1) an area of approximately 5 x 7 cm on the back of each animal was clipped.
- % coverage: The formulation was applied on an area of approx. 10 % of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females.
- Type of wrap if used: The formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with aluminium foil and elastic bandage. A piece of tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the dressings were removed, the skin was cleaned of residual test material using tap water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume or concentration used: Yes; 10 mL/kg body weight

VEHICLE
- Specific gravity: 0.92

- Preparation of dosing solutions: The preparations (w/w) were kept at room temperature and dosed within 4 hours after adding the vehicle to the test material. Homogeneity was obtained to visually acceptable levels and the formulations were stirred during dosing. Adjustment was made for specific gravity of the vehicle. No correction was made for purity of the test material. In order to obtain homogeneity, the formulations were heated in a water bath with a maximum temperature of 60.2 °C for 33 minutes. The formulations were allowed to cool down to a temperature of maximally 40 °C prior to dosing. Test material preparations were stirred on a magnetic stirrer during application.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Animals were observed for mortality/viability twice daily. Body weights were recorded on Days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: Yes. At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15 animals were observed for clinical signs. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No clinical signs were noted for the animals.
General erythema was noted for one female animal on Day 2.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Any other information on results incl. tables

Table 1: Body Weights (g)

Sex / Dose Level

(mg/kg)

Animal

Day 1

Day 8

Day 15

Males / 2000

1

370

372

391

2

327

325

349

3

315

323

346

4

320

331

345

5

315

319

334

Mean

329

334

353

St. Dev

23

22

22

N

5

5

5

Females / 2000

6

210

221

227

7

204

211

218

8

213

219

220

9

206

209

207

10

227

229

237

Mean

212

218

222

St. Dev

9

8

11

N

5

5

5

 

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 this study the LD50 value was found to exceed 2000 mg/kg bw.
Executive summary:

The potential of the test material to cause acute dermal toxicity in the rat was investigated in accordance with the standardised guidelines OECD 402, EU Method B.3, US EPA OPPTS 870.1200 and JMAFF 12 Nousan, Notification No 8147 under GLP conditions.

The test material was administered to five Wistar rats of each sex by a single dermal application in an occlusive fashion at a limit dose of 2000 mg/kg body weight for 24 hours. After the exposure period, dressings were removed and the skin cleaned of residual test material using tap water. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred and there were no clinical signs noted for the animals. However, general erythema was noted for one female animal on Day 2. The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.

No abnormalities were found at macroscopic post mortem examination of the animals.

Under the conditions of this study the LD50 value was found to exceed 2000 mg/kg bw.