Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The test substance is of low oral acute toxicity with an oral LD50 ( rat) of > 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:
2016-10-14 to 2016-11-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
(2001)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: CD / Crl: CD(SD)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Strain: Rat (Rattus norvegicus) / CD / Crl: CD(SD)
- Age at start of administration: Approx. 8 weeks
- Weight at start of administration: 189 - 220 g
- Fasting period before study: approx. 16 hours
- Housing: During the 14-day observation period the animals were kept in groups of 3 animals in MAKROLON cages (type III plus). Granulated
textured wood was used as bedding material for the cages.
- Diet:Commercial diet, ssniff® R/M-H V1534 (Certificates of analysis provided) ; discontinued approx. 16 hours before administration
- Water: tap water ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22°C ± 3°C
- Humidity (%): 55% ± 15%
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light (about 150 lux at approx. 1.50 m room height)
- Air change: 12 to 18-fold air change per hour



Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Route of administration Oral, by gavage
Selection of route of administration According to the OECD/EC guidelines
Administration volume 1.75 mL/kg b.w.
Dose levels 2000 mg/kg b.w.



DOSAGE PREPARATION: The test item was used as supplied.

CLASS METHOD (if applicable)
Principle of the ATC-test method
This procedure permits the identification of the 'acute-toxic-class' (ATC), a measure-ment of the acute toxicity by the oral route.

The test item is administered orally by gavage at a single dose level to a group of experimental animals. The dose used is selected from a series of defined dose levels. Due to the small number of animals used with this method, there is no need to perform a range finding test.
The test item is tested using a stepwise procedure, each step uses three female animals. The results of each step determine if:
o no further testing is needed,
o the next step will be performed with the same dose,
o the next step will be performed at the next higher or next lower dose level.

Starting at 2000 mg/kg b.w.
Three animals of one sex (preferably females) are treated at 2000 mg/kg b.w. (first step). If two to three animals die, testing at 300 mg/kg b.w. should be performed.
If no to one animal dies, the test item should be retested (second step) with 2000 mg/kg b.w., using three animals of the same sex.
If, in this second step, two to three animals die, testing at 300 mg/kg b.w. should be performed. If, in this second step, no to one animal dies, no further testing is necessary.
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
6 female animals 2000 mg/kg b.w.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours
after administration. All surviving animals were observed for a period of 14 days. Individual body weights were recorded before administration
of the testsubstance and thereafter in weekly intervals up to the end of the study.

- Other examinations performed: changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory,autonomic and central
nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter
each working day. Any tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma were also noted.

- Necropsy of survivors performed: At the end of the experiments, all animals were sacrificed, dissected and inspected macroscopically. All gross
pathological changes were recorded.

- No histopathology was carried out as no macroscopical findings were noted at autopsy.
Statistics:
No statistical analysis was performed as the method used is not intended to allow a calculation of a precise LD50 value.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Under the present test conditions, a single oral administration of 2000 mg test item/kg b.w. did not reveal any signs of toxicity.
Clinical signs:
Under the present test conditions, a single oral administration of 2000 mg test item/kg b.w. did not reveal any signs of toxicity.
Body weight:
All animals gained the expected body weight at the end of the study period.
Gross pathology:
No pathological changes were observed at necropsy.
Other findings:
- Histopathology:
No histopathology was carried out as no macroscopical findings were noted at autopsy.

no further information

Conclusions:
The LD50value was ranked exceeding 2000 mg/kg b.w.
Executive summary:

Aim of the experiment was to obtain information on the toxicity, in particular lethality, of the test item.

Acute toxicity, oral, in rats according to OECD guideline 423 and EC method B.1 tris - ATC method - was employed to establish the required information for hazard assessment and hazard classification.

In this experiment the test item was examined for acute toxicity after a single oral administration to rats. The test item was used as supplied.

Under the present test conditions, a single oral administration of 2000 mg test item/kg b.w. did not reveal any signs of toxicity.

All animals gained the expected body weight at the end of the study period.

No pathological changes were observed at necropsy.

The LD50value was ranked exceeding 2000 mg/kg b.w.

Test item

LD50[mg/kg b.w., p.o.]

24 hours

14 days

females

females

> 2000

> 2000

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study is valid without restriction (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

Justification for classification or non-classification

Based on the results of the acute oral study and according to the criteria of EC Regulation 1272/2008 the test substance has a low acute toxicity if swallowed (LD50 (rat) > 2000 mg/kg bw). Therefore, the test substance must not be classified.