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Description of key information

In a GLP study according to OECD TG 423 (acute toxic class method) with rats the LD 50 value of the test substance was determined as > 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:
2016-10-04 to 2016-10-20
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
Remarks:
Crl:WI
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: TOXI COOP ZRT. Cserkesz u. 90., 1103 Budapest, Hungary
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks
- Weight at study initiation: 179 - 184 g
- Fasting period before study: 1 day
- Housing: group caging (3 rats/cage), Type II polypropylene/polycarbonate cages
- Diet: ad libitum, ssniff® SM R/M-Z+H complete diet for rats and mice produced by ssniff Spezialdiäten GmbH, 59494 Soest, Germany
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: 5-6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle: 10mL/kg bw
- Justification for choice of vehicle: standard vehicle
- Purity: aqua purificata Ph.Hg. VIII. from Parma Produkt Kft.

MAXIMUM DOSE VOLUME APPLIED: not specified

DOSAGE PREPARATION: Formulations were prepared just before the administration.

CLASS METHOD
- Rationale for the selection of the starting dose: The starting dose was selected on the basis of the available information about the test item and similar substances.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 females
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. 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
- Other examinations performed: clinical signs, appearance of tissue and organs
- experimental design: The study was performed in two consecutive steps with three rats per step.
Statistics:
not applicable
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred at 2000 mg/kg bw single oral dose of the test item. All female rats in step 1 and step 2 survived until the end of the 14-day observation period.
Clinical signs:
No symptoms were observed throughout the 14-day post-treatment period at any groups of the female animals.
Body weight:
The mean body weight of the animals corresponded to their species and age throughout the study.
Gross pathology:
All animals survived until the scheduled necropsy on Day 15.
Severe hydrometra was detected in two animals of group 2 and moderate hydrometra was found in one female of the group 1, as well. Hydrometra is physiological finding and connected to the cycle of the animal.
No further pathological changes were found during the macroscopic examination of animals.
Other findings:
none
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the test item was determined to be above 2000 mg/mg bw in female rats after oral application.
Executive summary:

The acute oral toxicity of the substance was investigated in a GLP study according to OECD TG 423. The objective of the study was to assess the toxicity of test item when administered in a single dose to rats at one or more defined dose levels. The starting dose was selected on the basis of the available information about the test item and similar substances. The 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. No animal died in the first step at 2000 mg/kg bw dose level, so 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, as the stopping criteria of Annex 2d of OECD TG 423 was met.


Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out 15th day after the treatment in all animals. No death occurred at 2000 mg/kg bw single oral dose of the test item. All female rats survived until the end of the 14-day observation period. No symptoms were observed throughout the 14-day post-treatment period at any groups of the female animals. The body weight development was undisturbed in all animals. All organs of the animals treated with 2000 mg/kg bw proved to be free of treatment related gross pathological changes. In conclusion, the LD50 of the test item was considered to be above 2000 mg/kg body weight by oral route in the rat.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The only available study is of high quality and reliable without restrictions.

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

The acute oral toxicity of the substance was investigated in a GLP study according to OECD TG 423. The objective of the study was to assess the toxicity of test item when administered in a single dose to rats at one or more defined dose levels. The starting dose was selected on the basis of the available information about the test item and similar substances. The 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. No animal died in the first step at 2000 mg/kg bw dose level, so 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, as the stopping criteria of Annex 2d of OECD TG 423 was met.


Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out 15th day after the treatment in all animals. No death occurred at 2000 mg/kg bw single oral dose of the test item. All female rats survived until the end of the 14-day observation period. No symptoms were observed throughout the 14-day post-treatment period at any groups of the female animals. The body weight development was undisturbed in all animals. All organs of the animals treated with 2000 mg/kg bw proved to be free of treatment related gross pathological changes. In conclusion, the LD50 of the test item was considered to be above 2000 mg/kg body weight by oral route in the rat.

Justification for classification or non-classification


Classification, Labelling, and Packaging Regulation (EC) No 1272/2008


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 toxicity according to Regulation (EC) No 1272/2008 (CLP), as amended for the fifteenth time in Regulation (EU) 2020/1182.