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Administrative data

Description of key information

rat, oral, OECD 423, class method, limit test, LD50 > 2000 mg/kg bw

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:
2017-09-12 to 2017-09-28
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:
December 17, 2001
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
OGYÉI- National Institute of Pharmacy and Nutrition (21.04.2016)
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
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks old in first and second step
- Weight at study initiation: 191 - 196 g (first step), 201 - 204 g (second step)
- Fasting period before study: The day before treatment the animals were fasted. The food but not water was withheld overnight. The food was given back 3 hours after the treatment.
- Housing: Group caging (3 animals/cage)
- 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, ad libitum
- Acclimation period: 12 days in first step and 13 days in second step

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): above 10 air exchanges/hour by central air-condition system.
- Photoperiod (hrs dark / hrs light): 12 hours dark/ 12 hours light, from 6.00 a.m. to 6.00 p.m. light period
Route of administration:
oral: gavage
Vehicle:
methylcellulose
Remarks:
1 % in Aqua purificata
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Lot/batch no. (if required): AX4380542

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Starting dose was selected on the basis of the available information about the test item.
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, the stopping criteria of Annex 2d of OECD Guideline No. 423 was met.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Body weight measurement: Day 0, 7, 15;
Clinical observation: At least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h after the treatment, and once a day for 14 days thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, grosspathology, lethality, other: General state, external appearance, behaviour
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
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:
other: In group 1 and group 2 treated with 2000 mg/kg bw dose no treatment related symptoms were observed throughout the 14-day post-treatment period.
Gross pathology:
All animals treated with 2000 mg/kg bw dose survived until the scheduled necropsy on Day 15.
Internal necropsy finding as pale kidneys was observed in animal No.: 7023 of group 1 and in animal No.: 7037 of group 2. This alteration could not be related to the test item toxic effect, but was regarded an individual variation. Most likely the observation is a congenital anomaly. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals treated with 2000 mg/kg bw dose.
Interpretation of results:
other: EU GHS criteria not met
Conclusions:
No death occurred after the single 2000 mg/kg bw oral dose of the test item. There were no toxic clinical signs and any to the test item related effect in body weights and body weight gains during the study.
Autopsy revealed no treatment related pathological changes. The method used is not intended to allow the calculation of a precise LD50 value (LD50 > 2000 mg/kg bw).
Executive summary:

The determination of the acute oral toxicity of the test item was conducted following OECD Guideline 423 under GLP compliance. 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, the stopping criteria of Annex 2d of OECD Guideline No. 423 were met.

No death occurred after the single 2000 mg/kg bw oral dose of the test item. There were no toxic clinical signs and any to the test item related effect in body weights and body weight gains during the study. Autopsy revealed no treatment related pathological changes. The method used is not intended to allow the calculation of a precise LD50 value (LD50 exceeded 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:
OECD guideline study under GLP compliance

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

The determination of the acute oral toxicity of the test item was conducted following OECD Guideline 423 under GLP compliance. 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, the stopping criteria of Annex 2d of OECD Guideline No. 423 were met.

No death occurred after the single 2000 mg/kg bw oral dose of the test item. There were no toxic clinical signs and any to the test item related effect in body weights and body weight gains during the study. Autopsy revealed no treatment related pathological changes. The method used is not intended to allow the calculation of a precise LD50 value (LD50 exceeded 2000 mg/kg bw).

Justification for classification or non-classification

In an acute oral toxicity study according to OECD Guideline 423 (acute toxic class method) with the test item, an LD50 > 2000 mg/kg bw in rats has been determined, hence the registered substance is not classified for acute toxicity in accordance with Regulation (EC) No 1272/2008.