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Description of key information

Acute toxicity: oral


Key study: Method according to OECD 420, GLP study. The LD50 of the test item is higher than 2000 mg/ kg body weight by oral route in the rat.

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:
01 September 2020 to 16 September 2020
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevage JANVIER LABS (53940 Le Genest St Isle –
France)
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8weeks
- Weight at study initiation: The animals were weighed on day D0 (just before administering the test item) then on D2, D7, and on D14.
- Fasting period before study: Day 1, food available 4 hours after test item administration
- Housing: group of three in solid-bottomed clear polycarbonate cages with a
stainless-steel mesh lid. Each cage contains sawdust bedding which was changed at least 2 times a week. Each cage was installed in conventional air-conditioned animal husbandry.
- Diet (e.g. ad libitum): foodstuff (ENVIGO - 2016) were supplied ad libitum. Food was removed on D-1 and then redistributed 4 hours after the test item administration
- Water (e.g. ad libitum): Drinking water (tap-water from public distribution system) was supplied ad libitum
- Acclimation period: at least 5 days

- Method of randomisation in assigning animals to test and control groups

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): 10x/hr
- Photoperiod (hrs dark / hrs light): 12hrs dark / 12 hrs light

IN-LIFE DATES: From: 01 September 2020 To: 16 September 2020
Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 1.0057g/5ml and 2.0053/10ml
- Amount of vehicle (if gavage): 10ml/kg
- Justification for choice of vehicle: it produced the most suitable formulation at the requested concentration


MAXIMUM DOSE VOLUME APPLIED: 2000mg/kg, 10ml/kg


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As no excessive systemic toxicity of the test item was anticipated at the dose of 2000 mg/kg body weight, the first test dose was 2000 mg/kg body weight
Doses:
2000mg/kg bw
No. of animals per sex per dose:
Preliminary:1 female
Main: 4 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (or other?) 14 days
- Frequency of observations and weighing: The animals were weighed on day D0 (just before administering the test item) then on D2, D7, and on D14. Systematic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions at 30 minutes, 1 hour, 3 hours, 4 hours, on day 1 and day 2 and during 14 days following the administration of the test item
- Necropsy of survivors performed: yes
- Clinical signs including body weight : were recorded
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Spontaneous activity, Preyer’s reflex (noise), Respiratory rate, Convulsions, Tremors, Body temperature, Muscle tone, Palpebral opening, Pupil appearance, Salivation, Lachrymation, Righting reflex and Back hair appearance, MORTALITY, BODY WEIGHT EVOLUTION, Organ observations
Statistics:
Not performed
Preliminary study:
Preliminary Study at 2000mg/kg bw did not produce any signs of toxicity in a single female rat. According to this result, 4 more female rats recieved the same dose of 2000mg/kg bw. 
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:
No abnormalities
Gross pathology:
Nothing to report

Body Weight and gains in grams






















































FEMALES



D0



 



D2



D2-D0



D7



D7-D0



 



D14



D14-D0



Rf 5165



187



 



201



14



222



35



 



247



60



Rf 5166 Rf 5167 Rf 5168 Rf 5169



182 205 210 208



 



190 210 222 231



8 5


12 23



215 233 250 247



33 28 40 39



 



232 251 265 269



50 46 55 61



MEAN


Standard deviation



198.4


12.9



 



210.8


16.3



12.4


6.9



233.4


15.2



35.0


4.8



 



252.8


14.8



54.4


6.4


Interpretation of results:
other: Not classified (CLP Regulation EC no. 1272/2008).
Conclusions:
The LD50 of the test item is higher than 2000 mg/ kg body weight by oral route in the rat.
Executive summary:

The oral acute toxicity of the test item was determined according to OECD Guideline 420 under GLP conditions. As no excessive systemic toxicity of the test item was anticipated at the dose of 2000 mg/kg body weight, the first test dose was 2000 mg/kg body weight. A single female 8 week old non-pregnang and nulliparous Sprague Dawley rat recieved 2000mg/kg bw via oral gavage in DMSO. No signs of toxicity were noted and 4 further female rats recieved the same dose of 2000mg/kg. No mortality occured during the study. No clinical signs or abnormal changes in body weight were recorded. The macroscopic examination of the animals at the end of the study did not reveal treatment related changes. Thus, the LD50 of the test item is higher than 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 study has a Klimisch score of 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

Acute Toxicity: Oral


The oral acute toxicity of the test item was determined according to OECD Guideline 420 under GLP conditions. As no excessive systemic toxicity of the test item was anticipated at the dose of 2000 mg/kg body weight, the first test dose was 2000 mg/kg body weight. A single female 8 week old non-pregnang and nulliparous Sprague Dawley rat recieved 2000mg/kg bw via oral gavage in DMSO. No signs of toxicity were noted and 4 further female rats recieved the same dose of 2000mg/kg. No mortality occured during the study. No clinical signs or abnormal changes in body weight were recorded. The macroscopic examination of the animals at the end of the study did not reveal treatment related changes. Thus, the LD50 of the test item is higher than 2000 mg/ kg body weight by oral route in the rat.

Justification for classification or non-classification

Based on available information (LD higher than 2000mg/kg bw orally in rats) the substance is not classified (CLP Regulation EC no. 1272/2008)

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