Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 - 28 Mar 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted in 2001
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Slovenska Narodna Akreditacna Sluzba, Bratislava, Slovenska Republika
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

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: 9 - 10 weeks
- Weight at study initiation: 172 - 195 g (step 1), 193 - 204 g (step 2)
- Fasting period before study: animals were fasted over-night prior to administration and after administration for further 3 - 4 h
- Housing: 3 animals per cage in plastic cages suspended on stainless steel racks on Lignocel S3/4 bedding (Lufa-ITL GmbH, Germany)
- Diet: laboratory food ssniff (Spezialdiäten GmbH, Germany) was offered at recommended doses each day approximately at the same time (analyses were performed)
- Water: tap water, ad libitum (analyses were performed)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.09 ± 0.21
- Humidity (%): 54.33 ± 2.34
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: standard vehicle according to OECD TG 423

DOSAGE PREPARATION: The required amount of the test item (according to the body weight and dose) was mixed with vehicle (olive oil) shortly before administration

Doses:
2000 mg/kg bw (step 1 and 2)
No. of animals per sex per dose:
3 females per step (2 steps)
Control animals:
no
Remarks:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed individually immediately after administration of the test item and 0.5, 1, 2 and 4 hours later. Each animal was inspected daily for the next 14 days. Observations included: changes in skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity, and behavioural pattern. Particular attention was given to potential neurologic endpoints such as tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Body weights were determined immediately prior to administration of the test item and weekly thereafter.
- Necropsy of survivors performed: yes

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
Animals displayed no signs of intoxication, change of health, nor any other adverse reaction.
Body weight:
Normal body weight gains were observed in all animals.
Gross pathology:
No macroscopic findings were observed in any animal.

Any other information on results incl. tables

Table 1: Absolute body weights and body weight gain

Step  Animal No. Starting dose (mg/kg bw) Body weight (g) Body weight gain (week 2 - Initial (g)
Initial Week 1 Week 2
1 1 2000 179 203 220 41
2 195 198 202 7
3 172 188 203 31
2 4 193 194 201 8
5 206 219 234 28
6 204 222 230 26

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:
In this acute oral toxicity study a LD50 value > 2000 mg/kg bw in female rats was found.