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Description of key information

GLP compliant OECD 423: LD50 (oral) > 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:
Nov 19, 2019 - Feb 12, 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:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Janvier Labs SAS CS 4105 LE Genest St Isle 53941 Saint Berthevin Cedex / France
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at start of study: 8-11 weeks
- Weight at study initiation: 192.66 g (SD 4.4)
- Fasting period before study: overnight fasting prior to dosing
- Housing: separately in type IV Makrolon cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 24.0°C
- Humidity (%): 45 – 65%
- Photoperiod (hrs dark / hrs light): 12 hour light - 12 hour dark regime

IN-LIFE DATES: From: day 1 To: day 15
Route of administration:
oral: gavage
Vehicle:
corn oil
Remarks:
Methocel K4M Premium solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 and 200 g/L
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: well tolerated and established standard vehicle

MAXIMUM DOSE VOLUME APPLIED: 1 mL/100 g
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
300 mg/kg bw: 1 (f)
2000 mg/kg bw: 5 (f)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: day 1, 2, 4, 6, 8, 11, 13 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
Standard statistical methods have been applied for data processing.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was seen in rats treated with 2000 mg/kg bw.
Clinical signs:
There were no clinical signs of reaction to treatment with 2000 mg/kg.
Body weight:
The animal showed expected gains in body weight over the observation period.
Gross pathology:
The gross pathological examination revealed no organ alterations.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present study, it is concluded that the test item has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg bw after single oral administration in female rats.
Executive summary:

Objective

The objective of the present study was to identify potential toxic effects of the test item after single oral administration to rats in a stepwise procedure.

Study Design

Following a sighting test at dose levels of 300 mg/kg b.w. and 2000 mg/kg b.w. in one female rat per dose group, a further group of four fasted females was given a single oral dose of the test material, as a formulation in corn oil, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored in all animals during the study. All animals were subjected to gross necropsy.

Results

Mortality: There were no deaths.

Clinical Observations: Transient piloerection was noted 4 hours after dosing in the animal treated at a dose level of 300 mg/kg. There were no signs of systemic toxicity noted in the remaining animals.

Body Weight: All animals showed expected gains in body weight.

Necropsy: The uterus of the animal treated with 300 mg/kg was filled with liquid, indicative of unspecific changes during the physiological oestrous cycle. There were no signs of abnormalities noted at necropsy in the remaining animals.

Conclusion

Under the conditions of the present study, it is concluded that the test item has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg bw after single oral administration in female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Guideline study under GLP conditions

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 provided information the test item is not classified for acute oral toxicity according to the EU Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures.