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Description of key information

A key study for acute oral toxicty according to toxic class method resulted in in LD >2000 mg/kg bw and did not show any clinical observations, body weight changes or gross pathological changes at limit dose.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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.
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
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)
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.
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.
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.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Klimisch 1

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A key acute oral toxicity study according to toxic class method was available with the use of 2000 mg/kg bw as the starting dose in three female rats, followed by another three female rats (Kuthy, 2012). No animal died in the first and second step, neither were there any clinical symptoms.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. LD50was above 2000 mg/kg bw.

This key study overruled the existing information providing an LD50 of 900 mg/kg, however the latter source was based on the information provided in the MSDS and was not assignable. The new LD50 >2000 mg/kg based on state of the art method will be applied.


Justification for selection of acute toxicity – oral endpoint
Key study

Justification for classification or non-classification

As LD50 was above limit dose of 2000 mg/kg bw for oral application, the test substance does not need to be classified and has no obligatory labelling requirement for acute oral toxicity according to the EC Directive (No.93/21/EEC) and CLP (No. 1272/2008 of 16 December 2008).

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