Registration Dossier

Administrative data

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

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 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

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:
male/female
Details on test animals 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

Administration / exposure

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.

Results and discussion

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..
Effect levels
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.

Applicant's summary and conclusion

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.