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Description of key information

The acute toxicity of the test item was determined in a GLP-study according to OECD Test Guideline 423 as LD50 > 2000 mg/kg bw (reference 7.2.1 -1).

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:
09 October 2012 to 11 December 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
17 December 2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
30 May 2008
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
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: 8 weeks
- Weight at study initiation: 174g - 202g
- Fasting period before study: 1 day
- Housing: Group caging (3 animals/cage)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 13-14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 8-12
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: Starting 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:
6 females (in two step of 3)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed individually after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h after the treatment and twice each day for 14 days thereafter. 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
- Other examinations performed: clinical signs, body weight,histopathology
Statistics:
not applicable
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
none
Body weight:
The mean body weight of the other animals corresponded to their species and age throughout the study.
Gross pathology:
All animals survived until the scheduled necropsy on Day 15.
No pathological changes were found related to the effect of the test item during the macroscopic examination of animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute toxicity of the test item was determined in a GLP-study according to OECD Test Guideline 423 as LD50 > 2000 mg/kg bw.
Executive summary:

An acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats to evaluate the acute oral toxicity of the test item. No animal died in the first step at 2000 mg/kg bw dose level, therefore 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 (presented in Appendix VII) was met. Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out on the 15th day 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.

In conclusion, the LD50 of the test item is > 2000 mg/kg.bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
GLP study according to OECD TG, RL1.

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

Acute oral toxicity study

An acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats to evaluate the acute oral toxicity of the test item (reference 7.2.1 -1). No animal died in the first step at 2000 mg/kg bw dose level, therefore 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 (presented in Appendix VII) was met. Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out on the 15th day 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. In conclusion, the LD50 of the test item is > 2000 mg/kg.bw.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute oral toxicity, the test item is not classified for acute oral toxicity according to Regulation (EC) No 1272/2008 (CLP), as amended for the twelfth time in Regulation (EU) 2019/521.

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