Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to GLP and valid methods and is considered relevant and reliable for classification.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethyl trichloroacetate
EC Number:
208-212-7
EC Name:
Ethyl trichloroacetate
Cas Number:
515-84-4
Molecular formula:
C4H5Cl3O2
IUPAC Name:
ethyl 2,2,2-trichloroacetate
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): Ethyl trichloroacetate
- Substance type: Organic, monoconstituent substance
- Physical state: Colourless, liquid
- Analytical purity: 99.9%
- Impurities (identity and concentrations): See confidential details
- Composition of test material, percentage of components: See confidential details
- Purity test date: CoA, dated October 04,2012
- Lot/batch No.: DEFM114019
- Expiration date of the lot/batch: 2014-09-07
- Stability under test conditions: Stable
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
other: Crl:(WI)BR
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: TOXI COOP ZRT. Cserkesz u. 90, 1103 Budapest, Hungary
- Age at study initiation: Young adult rats, 8 weeks old in first and second step
- Weight at study initiation: 200-204 g (first step); 198-202 g (second step)
- Fasting period before study: The day before treatment the animals were fasted. The food but not water was withheld overnight. Animals were weighed before the application and the food was given back 3 hours after the treatment.
- Housing: 3 animals/cage in Type II polypropylene/polycarbonate cage; laboratory bedding
- Diet (e.g. ad libitum): ssniff® SM R/M-Z+H complete diet for rats and mice produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany, ad libitum
- Water (e.g. ad libitum): Tap water from municipal supply, as for human consumption from bottle ad libitum
- Acclimation period: 6 days in first step and 7 days in second step

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 8-12 (by central air-condion system)
- Photoperiod (hrs dark / hrs light): Artificial light from 6 a.m. to 6 p.m.

IN-LIFE DATES: From: October 18, 2012 To: November 8, 2012 (first group) and November 9, 2012 (second group)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
vegetable oil
Remarks:
sunflower oil
Details on oral exposure:
VEHICLE Helianthi annui oleum raffinatum (sunflower oil)
- Concentration in vehicle: The test item was applied in a concentration of 200 mg/mL.
- Amount of vehicle (if gavage): Concentration was adjusted to maintain a treatment volume of 10 mL/kg bw.
- Lot/batch no. (if required): 19/4

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw.

DOSAGE PREPARATION (if unusual): All doses were formulated in the vehicle. Concentration was adjusted to maintain a treatment volume of 10 mL/kg bw. The test item was applied in a concentration of 200 mg/mL. Formulations were prepared just before administration and stirred continuously during the treatment.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Staring dose was selected on the basis of the available information about the test item.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 females in the first step, 3 females in the second step
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality:
Animals were observed individually after dosing at least once during the first 30 minutes, then 1h, 2h, 3h, 4h after the treatment and twice each day for 14 days thereafter.
Clinical signs:
Individual observations were performed on the skin and fur, eyes and mucous membranes and also 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.
Body weight:
The body weights were recorded on day 0 (just before the treatment), on day 7 and on day 15 with a precision of 1 g.
- Necropsy of survivors performed: yes. At the end of the observation period all rats were sacrified under isofluran anaesthesia. After examination of the external appearance, the cranial, thoracic and abdominal cavities were openend and the appearance of the tissues and organs was observed, and any abnormality was recorded with details of its location, colour, shape and size.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No lethality was noted at single oral dose of Ethyl Trichloroacetate at 2000 mg/kg bw. All female rats in step 1 and step 2 survived the end of the 14-day observation period.
Clinical signs:
No treatment related symptoms were observed on the day of the treatment and during the 14-day observation period, the general state and behaviour of experimental animals were normal.
Body weight:
The body weight development was undisturbed in all animals.
Gross pathology:
All animals survived until the scheduled autopsy on day 15. Pale kidneys were observed in animal No. 5682 as internal gross pathological finding. This macroscopic alteration could not be related to the test item toxic effect; it could be regarded as individual variation. It is a congenital anomaly, probably.
No pathological changes were found related to the effect of the test item during the macroscopic examination of animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 > 2000 mg/kg bw.
Executive summary:

An acute toxic class method study was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animals died in the first step at 2000 mg/kg bw dose level, therefore the treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 was met. Animals were weighed, observed for lethality and toxic symptoms for 14 days after treatment. Gross pathological examination was carried out on the 15thday after the treatment. No lethality was noted at single oral dose of 2000 mg/kg bw. No clinical symptoms were observed on the day of the treatment and during the 14-day observation period, the general state and behaviour of experimental animals were normal. The body weight development was undisturbed in all animals. All animals survived until the scheduled autopsy on day 15. All organs of all experimental animals proved to be free of treatment related gross pathological changes. LD50 was above 2000 mg/kg bw.