Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15.3.-13.4.2010
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.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Carbolic oil
- Substance type: mixture of organic compounds
- Physical state: brown oil-like liquid
- Composition of test material, percentage of components: Main components (by GC) - Indene 17.27 % (w/w), Phenol 13.94 % (w/w), Indane 12.86 % (w/w), Naphthalene 10.54 % (w/w), m-Cresol 8.79 % (w/w), p-Cresol 4.87 % (w/w), o-Cresol 4.49 % (w/w), m-/p-Xylene 3.03 % (w/w), 1,3,5-Trimethylbenzene 1.52 % (w/w), 3-Ethyltoluene 1.41 % (w/w), Toluene 1.33 % (w/w), Ethylbenzene 1.18 % (w/w), 1,2,4-Trimethylbenzene 1.52 % (w/w), Coumarone 1.57 % (w/w), 28 other hydrocarbons from 0.1 up to 1.0 % (w/w), 14 other hydrocarbons up to 0.1 % (w/w)
- Lot/batch No.: Composite sample No. 3, ATE No. 10438
- Expiration date of the lot/batch: 08/2022
- Stability under test conditions: stable
- Storage condition of test material: The sample will be stored in supplied metal container in dry room at the temperature < 30°C.

Test animals

Species:
rat
Strain:
Wistar
Sex:
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
- Age at study initiation: 8-10 weeks at the time application
- Fasting period before study: about 20 hrs
- Housing: animal room with monitoring conditions – 3 animals of one sex in one plastic breeding cage. Because of repulsive smell of the test substance the animals were transferred to laminar box from on 3rd day after application – 3 animals of one sex in one plastic breeding cage.
- Diet (e.g. ad libitum): ST 1 BERGMAN – standard pelleted diet ad libitum
- Water (e.g. ad libitum): drinking tap water ad libitum
- Acclimation period: at least 5 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + 3°C, permanently monitored
- Humidity (%): 30 – 70 %, permanently monitored
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12-hour light/12 hour dark

STUDY TIME SCHEDULE
Animal supply: 24. 02. 2010
Experimental part of study: 15. 03. - 13. 04. 2010

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Lot/batch no. (if required): 4726901

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Testing schedule (according to EU Method B.1 tris Annex 1D)
START: 2000 mg/kg – 3 females (Step No.1): no deaths ► 2000 mg/kg – 3 females, (Step No. 2): death of one female ► END of study
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations:
Body weight: before application, the 8th day and before euthanasia of animals
Mortality: daily
Clinical examination: daily
- Necropsy of survivors performed: yes (gross necropsy)

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The test substance administered at the dose of 2000 mg/kg caused death of one female.
Clinical signs:
Clinical signs of intoxication (various changes) were observed in all six animals at the 1st and 2nd day after application. At the 3rd day after application no clinical signs of intoxication were observed in all surviving animals.
Body weight:
Weight increments were adequate to species, sex and age of animals in experiment.
Gross pathology:
Pathologic macroscopic changes (Digestive tract - test substance in chymus; partial autolysis of organs) were observed in died female (No.6). Pathologic macroscopic changes (stomach - marked mucosal plicas; kidney – change of colour) were diagnosed during pathological examination in two animals.
Other findings:
- Histopathology:
Pathologic macroscopic changes (Digestive tract - test substance in chymus; partial autolysis of organs) were observed in died female (No.6). Histopathological examination of damaged organs was performed. Histopathological findings (liver – partial autolysis, centrolobular focal necrosis; stomach - partial autolysis; forestomach - partial autolysis; focal ulceration and focal polynuclear infiltration of mucous membrane) were observed.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the study results the value of LD50 of the test substance, Carbolic Oil, (in female rats) is higher than 2000 mg/kg of body weight.
Executive summary:

The test substance administered at the dose of 2000 mg/kg caused death of one female (No.6) in the group No.2 at the 3rd day morning after application.

Clinical signs of intoxication (various changes) were observed in all six animals at the 1st and 2nd day after application. At the 3rd day after application no clinical signs of intoxication were observed in all surviving animals.

Pathologic macroscopic changes (Digestive tract - test substance in chymus; partial autolysis of organs) were observed in died female (No.6). Histopathological examination of damaged organs was performed. Histopathological findings (liver – partial autolysis, centrolobular focal necrosis; stomach - partial autolysis; forestomach - partial autolysis; focal ulceration and focal polynuclear infiltration of mucous membrane) were observed.

Pathologic macroscopic changes (stomach - marked mucosal plicas; kidney – change of colour) were diagnosed during pathological examination in two animals.

According to the study results the value of LD50 of the test substance for female rats is higher than 2000 mg/kg of body weight.