Registration Dossier

Administrative data

Description of key information

Under the conditions of the study, the acute LD50 value of the test material was found to be > 2000 mg/kg bw in female Crl:WI rats.

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:
23 May 2017 to 7 June 2017
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)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (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:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks old
- Weight at study initiation: 182-199 g
- Fasting period before study: overnight before treatment and three hours following treatment
- Housing: 3 animals/Type II polypropylene/polycarbonate cages
- Diet: ad libitum
- Water: tap water ad libitum
- Acclimation period: 5-6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20.-25.0°C
- Humidity: 31-62%
- Air changes: 15-20 per hr
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: 23 May 2017 to 7 June 2017
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: selected by the Study Director to be that which is most likely to produce mortlaity in some dosed animals.
Doses:
2000 mg/kg/bw
No. of animals per sex per dose:
Two groups of three females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed on all animals at 30 min, 1, 2, 3, 4 and 6 hours after dosing and daily thereafter. Body weight was recorded on the day before treatment (day -1), the day of treatment (day 0) and weekly thereafter.
- Necropsy of survivors performed: yes. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other:
Clincal observations were performed on the skin, fur, eyes, mucous membranes, 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.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal in the confirmatory group
Clinical signs:
Reddish coloured faeces were observed 6 hours after treatment and on the day after treatment. Reddish coloured urine was observed on the day after treatment. Besides this, there were no systemic clinical signs noted in any animal throughout the study.
Body weight:
There were no treatment related body weight changes. However, slight bodyweight loss was observed in one rat during the first week of observation. Body weight gains of treated animals during the study showed no indication of a test material-related effect.
Gross pathology:
There was no evidence of the macroscopic observations at necropsy in the surviving animals.

The following observations were recorded in the animal found dead: dark red diffuse discolouration of all lobes of the non-collapsed lungs, reddish foamy material in the trachea, red liquid material mixed with the diet in the digestive content of the stomach, duodenum, jejunum, ileum and cecum.
Interpretation of results:
other: Not classified according to EU criteria
Conclusions:
Under the conditions of the study, the acute LD50 value of the test material was found to be > 2000 mg/kg bw in female Crl:WI rats.
Executive summary:

The single-dose oral toxicity of the test material was performed according to the acute toxic class method in line with standardised guidelines OECD 423 and EU Method B.1 tris and under GLP conditions.

During the study two groups of three female Crl:WI rats were treated with the test material at a dose of 2000 mg/kg bw (Group 1 and 2). A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after treatment. The test material was administered formulation in PEG 400 at a concentration of 200 mg/mL at a dose volume of 10 mL/kg bw. Initially, three females (Group 1) were treated at 2000 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. Only one death was observed in the confirmatory group; therefore no further testing was required in line with the guidelines. Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on days -1, 0, 7 and 14 (before necropsy). All animals were subjected to a necropsy and a macroscopic examination.

The test material caused one mortality in one animal out of six. Reddish coloured faeces were observed 6 hours after treatment and on the day after treatment. Reddish coloured urine was observed on the day after treatment. There were no additional clinical symptoms observed in any animal during the study. There were no treatment-related body weight changes. However, slight body loss was observed in one animal during the first week of observation. Body weight gains of treated animals during the study showed no indication of a test material-related effect. There was no evidence of the macroscopic observations at necropsy in any of the surviving animals. The following observations were recorded in the animals found dead: dark red diffuse discolouration of all lobes of non-collapsed lungs, reddish foamy material in the trachea, red liquid material mixed with the diet in the digestive contents of the stomach, duodenum, jejunum, ileum and cecum.

Under the conditions of the study, the acute LD50 value of the test material was found to be > 2000 mg/kg bw in female Crl:WI rats.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
One study assigned a Klimisch score of 1 is available.

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 single-dose oral toxicity of the test material was performed according to the acute toxic class method in line with standardised guidelines OECD 423 and EU Method B.1 tris and under GLP conditions.

During the study two groups of three female Crl:WI rats were treated with the test material at a dose of 2000 mg/kg bw (Group 1 and 2). A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after treatment. The test material was administered formulation in PEG 400 at a concentration of 200 mg/mL at a dose volume of 10 mL/kg bw. Initially, three females (Group 1) were treated at 2000 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. Only one death was observed in the confirmatory group; therefore no further testing was required in line with the guidelines. Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weight was measured on days -1, 0, 7 and 14 (before necropsy). All animals were subjected to a necropsy and a macroscopic examination.

The test material caused one mortality in one animal out of six. Reddish coloured faeces were observed 6 hours after treatment and on the day after treatment. Reddish coloured urine was observed on the day after treatment. There were no additional clinical symptoms observed in any animal during the study. There were no treatment-related body weight changes. However, slight body loss was observed in one animal during the first week of observation. Body weight gains of treated animals during the study showed no indication of a test material-related effect. There was no evidence of the macroscopic observations at necropsy in any of the surviving animals. The following observations were recorded in the animals found dead: dark red diffuse discolouration of all lobes of non-collapsed lungs, reddish foamy material in the trachea, red liquid material mixed with the diet in the digestive contents of the stomach, duodenum, jejunum, ileum and cecum.

Under the conditions of the study, the acute LD50 value of the test material was found to be > 2000 mg/kg bw in female Crl:WI rats.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to acute oral toxicity.