Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 - 30 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 guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
17 December 2001
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Slovak National Accreditation Service, Karloveska 63, 840 00 Bratislava 4, Slovak Republic
Test type:
acute toxic class method
Limit test:
yes

Test material

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

Test animals

Species:
rat
Strain:
Wistar
Sex:
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: 180 - 205 g
- Fasting period before study: over night and 3 - 4 h post-administration
- 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 - 30 August 2017

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: Olive oil is a standard vehicle according to OECD 423
- 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, the limit dose of 2000 mg/kg body weight was used as a starting dose.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 females
Control animals:
no
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
- 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 levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 is cut-off according to OECD 423
Mortality:
All (6/6 females) animals survived the limit dose of 2000 mg/kg body weight.
Clinical signs:
During the observation period, no animals displayed signs of intoxication, change of health, or any other adverse reaction.
Body weight:
The body weight of all animals increased during the study. No body weight losses were observed between the first and second week after administration.
Gross pathology:
During necropsy, no macroscopic findings were observed.

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

205

210

215

5

10

5

2

185

190

200

5

15

10

3

190

190

200

0

10

10

4

190

200

205

10

15

5

5

190

200

210

10

20

10

6

180

210

220

30

40

10

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 oral administration to female Wistar rats.

Based on 'Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight' of OECD 423 it can also be concluded that the LD50 cut-off value is equal to or greater than 5000 mg/kg body weight after single oral administration to Wistar rats.