Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
3.8.2010 - 24.8.2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was carried out in accordance with internationally valid GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
Short-term increase of humidity during study (defect of an air-condition unit). The deviation did not influence the wellness of animals and the study results.
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tar, brown-coal, low-temp.
- Molecular formula: not known - UVCB substance
- Molecular weight: not known - UVCB substance
- Smiles notation: not known - UVCB substance
- InChl: not known - UVCB substance
- Substance type: technical product
- Physical state: viscous liquid
- Lot/batch No.: T201E
- Expiration date of the lot/batch: 31.3.2011
- Stability under test conditions: stable
- Storage condition of test material: The substance was stored in closed vessel in dry room at the temperature bellow 25ºC in dark

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., Koleč u Kladna, Czech Republic, RČH CZ 21760152
- Weight at study initiation: 229-257g (males), 213-229g (females)
- Housing: animal room with monitoring conditions – one animal in one plastic cage
- Diet: ST 1 BERGMAN – standard pelleted diet ad libitum
- Water: drinking tap water ad libitum
- Acclimation period: at least 5 days
- Bedding: sterilized shavings of soft wood
- Randomisation: according to the internal rule, at the start of the study the weight variation of animals was minimal and did not exceed +/- 20 % of the mean weight
- Identification of animals: colour marks on tail, each cage was marked with the number of study, number of animal, sex, name and dose of the test substance
- Health condition: certificate of good health condition – from breeding farm; no signs of diseases were observed at clinical check-in, during the acclimatisation period and before the start of study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature 22 +/- 3°C, permanently monitored
- Humidity (%): relative humidity 30 – 70 %, permanently monitored
- Photoperiod: 12 hours light/12 hours dark

Time schedule of observations:
Body weight: before application, 8th and 15th day of study
Mortality: daily
Clinical signs: daily
Pathological examination: 15th day of study

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 6x6 cm
- % coverage: approx. 10%
- Type of wrap: covered by mull and held in contact by plaster (strapping)

REMOVAL OF TEST SUBSTANCE
- the remains of the substance were wiped off by water
- Time after start of exposure: 24 hours

TEST MATERIAL
The substance was applied as such. The amount of test substance for each animal was weighed out (according to its body weight and the dose) immediately before application.

VEHICLE
no vehicle
Duration of exposure:
24 hours

Doses:
2000 mg/kg

No. of animals per sex per dose:
10 animals: 5 females+ 5 males

Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Weighing: The animals were weighed at the start of the study (before application), at 8th day and at the end of experiment (15th day).
- Observation:
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, nutritive condition, autonomic and central nervous systems, psychic activity, somatomotor activity, reactions to stimuli, function of respiratory, circulatory, digestive and urogenital system. Also presence of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma was carefully observed.
- Necropsy of survivors performed:
All test animals surviving to the end of study were sacrificed on the 15th day by prolonged ethereal narcosis, and gross necropsy was carried out. Nutritional state, body surface, body foramina, thoracic, abdominal and cranial cavity were evaluated.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 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

Clinical signs:
Without clinical changes

Body weight:
In males and in females, the weight increments were adequate to species and age of animals in the experiment. Only slight decreased body weight and body weight increment in 2 females were recorded.

Gross pathology:
No death of animals was observed during 14 days observation period.
No macroscopic changes were diagnosed.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Executive summary:

The test substance - Tar, brown-coal, low-temp.- was tested for the assessment of acute dermal toxicity using Wistar rats. Testing was performed according to the Method B.3 Acute Toxicity (Dermal), Council Regulation (EC) No.440/2008, published in O.J. L 142, 2008.

 

The study was performed as limit test: two groups of animals – 5 males and 5 females at the dose of 2000 mg/kg of body weight. The pre-test was performed with 1 male and 1 female from each group. After clinical observation of these pilot animals for 2 days after test substance application, the other animals of the group were dosed. The test substance was applied on the shaved skin of the test animals in delivered form for 24 hours. The test animals were observed 14 days after exposure test substance, afterwards they were sacrificed, and the necropsy for macroscopic examination of the organs was performed.

    

The test substance applied at the dose of 2000 mg/kg of body weight did not cause death of animals. No clinical signs of intoxication were observed in all animals. No macroscopic change was diagnosed during pathological examination in all animals.

    

According to the results of study, the value of LD50 (dermal) of the test substance - Tar, brown-coal, low-temp. - for rats of both sexes is higher than 2000 mg/kg of body weight.