Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 - 31 Aug 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
24 February 1987
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 434 (Acute Dermal Toxicity - Fixed Dose Procedure)
Version / remarks:
Proposal for a New Draft Guideline, May 2004
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Slovak National Accreditation Service, Karloveska 63, 840 00 Bratislava 4, Slovak Republic
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dobrá Voda, Slovak Republic
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 195 - 200 g (f), 220 - 230 g (m)
- Housing: 3 animals per cage
- Bedding: Lignocel S3/4, Lufa - ITL GmbH, Germany
- Diet: ssniff (Spezialdiäten GmbH, Germany), provided at recommended doses each day approximately at the same time
- Water: tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.18 ± 0.45
- Humidity (%): 55.40 ± 3
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: To: 15 - 31 August 2017

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
olive oil
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped and shaved dorsal area of trunk
- % coverage: approx. 10% of total body surface area
- Type of wrap if used: semi-occlusive dressing with non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing: residual test item was removed with lukewarm water
- Time after start of exposure: 24 h

VEHICLE
- Justification for choice of vehicle: Olive oil is a standard vehicle according to test guideline
- Lot/batch no.: L63417
- Expiry date: 06/2018
- Manufacturer: Oleificio Luca, Italy
- Storage temperature (°C): 20 ± 5

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Available information indicated that the test item is likely to be non-toxic with regard to acute toxicity. Hence, a limit dose of 2000 mg/kg body weight was used as a starting dose.
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: immediately after dosing, 0.5, 1, 2 and 4 h after administration, daily for the next 14 days
- Frequency of weighing: immediately prior to dosing and weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All 5/5 females and 5/5 males at the limit dose of 2000 mg/kg body weight survived.
Clinical signs:
Animals lived through observation period without signs of intoxication. Neither change of health nor negative reactions were observed.
Body weight:
The body weight of all females increased during the study, stagnation of body weight in two females between the first and second week was noticed.
Gross pathology:
All animals (5 females and 5 males) were necropsied. During necropsy, no macroscopic changes were noticed.

Any other information on results incl. tables

  Table 1: Body Weights and Body Weight Differences

 

Sex

Dose

ID

Body Weight (g)

Body Weight Difference (g)

Initial

Week 1

Week 2

Week 1 - Initial

Week 2 - Initial

Week 2 - Week 1

 

 

 

 

2000 mg/kg

1

195

205

210

10

15

5

2

200

200

225

0

25

25

3

200

200

215

0

15

15

4

200

220

220

20

20

0

5

195

210

210

15

15

0

 

 

 

 

2000 mg/kg

6

230

250

275

20

45

25

7

230

250

270

20

40

20

8

230

235

250

5

20

15

9

230

245

260

15

30

15

10

220

245

260

25

40

15

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
The LD50 of the test item has been determined to be greater than 2000 mg/kg body weight after single dermal administration to male and female Wistar rats.