Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19.06.2017 – 06.07.2017
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
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and batch No.of test material: Baoding 20161221
- Expiration date of the batch:20-12-2018
- Purity: 99.1%
- Purity test date: 21-12-2016

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Cool, dry area.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Breeding farm VELAZ s.r.o., Lysolaje, Czech Republic, RČH CZ 21760118
- Age at study initiation: 8 weeks
- Fasting: 20 hours
- Weight at study initiation: 152 - 188g
- Housing: Plastic breeding cage with shavings of soft wood
- Diet: Altromin for rats/mice, Manufacturer: Altromin Spezialfutter GmbH & Co. KG, Germany ad libitum
- Water: drinking water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 – 70 %
- Photoperiod (hrs dark / hrs light): light period 12-hour light/12 hour dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: The substance is insoluble in water
- Batch no. (if required): 8001526002 with expiration 02/2018 ( Dr. Kulich Pharma, s.r.o., Czech Republic)

Immediately before application the test substance was weighed, mixed with vehicle (Olive oil) and resulting suspension was administered to the stomach by tube. All prepared suspensions of the test substance in olive oil were mixed by magnetic stirrer during administration.

MAXIMUM DOSE VOLUME APPLIED: 1 mL/100 g

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: There was no information on the substance, so for animal welfare reasons a starting dose of 300 mg/kg body weight was used.

Doses:
300, 2000 mg/kg bw
No. of animals per sex per dose:
3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
Animals were weighed before application, at the 8th day of study and at the 15th day, before euthanasia of animals.
After application the animals were observed individually:

- the first day: twice (30 minutes and 3 hours after application)
- the second day: twice (in the morning and in the afternoon) and daily thereafter for 14 days.
Observations included changes in skin and fur, eyes, visible mucous membranes, behaviour of animals, somatomotor activity, reactions to stimuli, and presence of lacrimation, salivation and discharge from nostrils, function of respiratory, digestive and urogenital system.

- Necropsy of survivors performed: Yes; All test animals survived to the end of study were sacrificed on the 15th day and gross necropsy was carried out. Nutritious status, body surface, body foramina, thoracic, abdominal and cranial cavity were evaluated

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no mortalities at 300 or 2000 mg/kg bw.
Clinical signs:
No clinical signs of intoxication were detected at at 300 or 2000 mg/kg bw during the entire study
Body weight:
There was no effect on body weights at 300 or 2000 mg/kg bw.
Gross pathology:
No pathologic macroscopic changes were diagnosed during pathological examination at at 300 or 2000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral study (acute toxic class) in the rat, the LD50 (female) for UV-1084 was >2000 mg/kg bw.
Executive summary:

In an acute oral toxicity study (17-468), groups of Wistar female rats (3/sex) were given single oral doses of UV-1084 (99.1%) in olive oil at doses of 300 and 2000 mg/kg bw and observed for 14 days.

LD50 (female): >2000 mg/kg bw.

The test substance administered at the doses of 300 or 2000 mg/kg did not cause death of any animals. There was no effect on body weights at any dose. No clinical signs of intoxication were detected during the entire study at any dose. No pathologic macroscopic changes were diagnosed during the pathological examination at any dose.

This acute oral study is classified as acceptable. It does satisfy the guideline requirement for an acute oral study (OECD 401) in the rat.