Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June-August 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Colour: colourless
- Odour: odourless
- CAS-Number: 89-32-7
- Molecular formula: C10 H2 O6
- Molecular weight: 218.12
Specific details on test material used for the study:
- Batch number: NJC1506009
- Appearance: White crystals
- Manufacturing date: 11 June 2015
- Expiry date: 10 December 2016
- Storage conditions: Controlled room temperature (15-25°C, below 70 RH%), under inert gas, protected from humidity
- Safety precautions: Routine safety precautions (lab coat, gloves, safety glasses, face mask) for unknown materials were applied to assure personnel health and safety.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: young healthy adult rats
- Weight at study initiation: between 201 g and 249 g
- Fasting period before study: no data
- Housing: individual caging
- Diet (e.g. ad libitum): ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" from ssniff Spezialdiäten GmbH, D-59494 Soest, Germany
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8 – 25.0 °C
- Humidity (%): 34 – 70%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
The back of each animal was shaved (approximately 10% area of the total body surface) approximately 24 hours prior to treatment. The test item was applied as a single dose to the shaved skin and remained in contact with the skin for the 24-hour exposure period. The test material was dampened with sufficient water before application to ensure good contact with the skin. Sterile gauze pads were placed on the skin of rats to cover the test item. These gauze pads were kept in contact with the skin using a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 hours. At the end of the exposure period, the area of skin treated with the test item was washed with water of body temperature.
Duration of exposure:
24 hours
Doses:
The test item was not expected to be lethal at 2000 mg/kg bw. A limit test wastherefore performed.
No. of animals per sex per dose:
5 males and 5 females at 2000 mg/kg
Control animals:
no
Details on study design:
Clinical Observations:
Clinical observations were performed on the day of treatment at 1 and 5 hours after application of the test item and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Skin Irritation:
Adverse skin reactions at the site of application were recorded daily following the removal of the dressing.

Body Weight Measurement:
The body weights were recorded on Day 0 (before test item administration) and on Days 7 and 14 just before necropsy.

Necropsy:
Macroscopic examination was performed on all animals. The animals were sacrificed by exsanguination under pentobarbital anaesthesia (Euthanimal 40%). After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.
Statistics:
none

Results and discussion

Preliminary study:
No pre-test performed. The test item was not expected to be lethal at 2000 mg/kg bw. A limit test was therefore performed.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The test item did not cause mortality at the dose level of 2000 mg/kg bw.
Clinical signs:
Clinical Observations:
There were no systemic clinical signs noted in any animal throughout the study.

Local Dermal Signs:
No local dermal signs were observed after treatment with the test item during the 14 days observation period.
Body weight:
Body weight gains of test item treated animals during the study showed no indication of a test item-related effect.
Gross pathology:
There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the acute dermal median lethal dose (LD50 value) of the test item was found to be above 2000 mg/kg bw.
Executive summary:

An acute dermal toxicity study was performed in Wistar rats, in compliance with OECD Guideline No. 402. A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was applied as a single dermal 24-hour exposure followed by a 14-day observation period.. The test item did not cause mortality at the dose level of 2000 mg/kg bw. There were no systemic clinical signs noted in any animal throughout the study. No local dermal signs were observed after treatment with the test item during the 14 days observation period. Body weight gains of treated animals during the study showed no indication of a test item-related effect. There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw. In conclusion, the acute dermal median lethal dose (LD50 value) of the test item was found to be above 2000 mg/kg bw.