Registration Dossier

Administrative data

Description of key information

Acute oral toxicity LD50: >2000 mg/kg bw (OECD 423, GLP)

Acute dermal toxicity LD50: >2000 mg/kg bw (OECD 402, GLP)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
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
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.

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

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
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.
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.  

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
There is one key study with a Klimisch score of 1. The quality of the database is high.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
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.
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Breeding farm VELAZ s.r.o., Lysolajské údolí 15/53, 165 00 Prague 6, Czech Republic, RČH CZ 11760500
- Weight at study initiation: 239-274 g (males); 224-247g (females)
- 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
Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: back of animal
- % coverage: about 6 x 6 cm (approx. 10 % of the body surface)
- Type of wrap if used: The application site was covered by a gauze and held in contact by plaster (strapping).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: 24 hrs

TEST MATERIAL
The amount of test substance for each animal was weighed out (according to its body weight and the dose) immediately before application. The test substance in delivered form was applied on the depilated area of skin.

Duration of exposure:
24 hrs
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 and weighing:
The animals were weighed at the start of the study (before application), at 8th day and at the end of experiment (15th day). The mean body weight of the groups was calculated from individual body weights. Body weight increments were calculated from the body weight at the start of the study, during the first week and at the end of the study.

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 surviving to the end of study were sacrificed on the 15th day by diethyl ether narcosis and gross necropsy was carried out. Nutritional state, body surface, body foramina, thoracic, abdominal and cranial cavity were evaluated.
Preliminary study:
The study was performed as a limit test: two groups of animals – 5 males and 5 females at a dose of 2000 mg/kg of body weight. The pre-test was performed with 1 male and 1 female from each group. After the end of exposure of these pilot animals, the other animals of the group were dosed..
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
The test substance applied at a dose of 2000 mg/kg of body weight did not cause death of any animals.
Clinical signs:
No clinical signs of toxicity were observed during the entire study.
Body weight:
There were no effects on body weight throughout the study.
Gross pathology:
No macroscopic changes were diagnosed during pathological examination.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study in rats, the LD50 of UV-1084 was >2000 mg/kg bw.
Executive summary:

In an acute dermal toxicity study (17-459) groups of Wistar rats (5/sex) were dermally exposed (semi-occlusive) to UV-1084 (99.1%) for 24 hours. Animals were then observed for 14 days.

Dermal LD50 (Males/Females) = >2000 mg/kg bw

The test substance applied at a dose of 2000 mg/kg of body weight did not cause death of any animals. There were no effects on body weight throughout the study. No clinical signs of toxicity were observed during the entire study. No macroscopic changes were diagnosed during pathological examination.

This acute dermal study is classified as acceptable. It does satisfy the guideline requirement for an acute oral study (OECD 402) in the rat.  

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
There is one key study with a Klimisch score of 1. The quality of the database is high.

Additional information

There is one acute oral study in rats and one acute dermal study in rats.

Acute oral toxicity

In an acute oral toxicity study (OECD 423/GLP), 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.

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. The LD50 (female) was > 2000 mg/kg bw.

Acute dermal toxicity

In an acute dermal toxicity study (OECD 402/GLP) groups of Wistar rats (5/sex) were dermally exposed (semi-occlusive) to UV-1084 (99.1%) for 24 hours. Animals then were observed for 14 days.

The test substance applied at a dose of 2000 mg/kg of body weight did not cause death of any animals. There were no effects on body weight throughout the study. No clinical signs of toxicity were observed during the entire study. No macroscopic changes were diagnosed during pathological examination. The dermal LD50 (males/females) = >2000 mg/kg bw.

The results from these studies are acceptable to use in the human health hazard assessment.

 

Justification for classification or non-classification

Based on the available information in the dossier, the substance UV-1084 (CAS No. 14516-71-3) does not need to classified for acute toxicity or specific target organ toxicity - single exposure when the criteria outlined in Annex I of 1272/2008/EC are applied.