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Description of key information

According to OECD 423

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:
From 13 JULY 2018 to 12 DECEMBER 2018
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:
Annex 2c: Test procedure with a starting dose of 300 mg/kg body weight
Deviations:
yes
Remarks:
Relative humidity/temperature in the room where animals were housed was sporadically below/above the optimal range during the study period. This deviation was not considered to have any impact on the interpretation of the study results or to affect signif
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS Spain S.L.
- Females (if applicable) nulliparous and non-pregnant: [yes/no]
- Age at study initiation: 8 weeks old
- Weight at study initiation:
- Fasting period before study: 3-4h
- Housing: 3 rats/cage; Bedding material: Sodispan SR-CHOPO-T; Change of cage: at least once a week
- Diet (e.g. ad libitum): Ad libitum except for an overnight fast prior to dosing and approx. 3-4h afterwards
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-25ºC
- Humidity (%): 30-70%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12:12 hours

IN-LIFE DATES: From: 13.07.18 To: 01.08.18
Route of administration:
oral: gavage
Vehicle:
methylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.5%
- Amount of vehicle (if gavage): 10 ml
- Justification for choice of vehicle:
- Lot/batch no. (if required): SLBT8618
- Purity:

MAXIMUM DOSE VOLUME APPLIED: 10 ml

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
Doses:
300, 2000 mg/kg bw (female)
No. of animals per sex per dose:
6 controls, 3 in dose groups
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (or other?) 14 days
- Frequency of observations and weighing: Clinical observations in response to treatment were performed 30 minutes, 2h, and 4h post-administration and once daily thereafter during the 14-day observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Any visible clinical signs, discomfort and mortality were recorded. Clinical signs included changes in skin, fur, eyes and mucous membranes. Alterations in respiratory pattern, behaviour, posture, response to handling and the presence of abnormal movements were reported as well. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Statistics:
No statistical analysis was performed.
Preliminary study:
No evidence of toxcicity and mortality.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
95% CL:
ca. 100
Mortality:
Treatment related mortality records are detailed in the table below:
Step Group Dose (mg/kg) Deaths
1 A 300 0
2 B 300 0
Clinical signs:
None effect was detected at 300 mg/kg bw dose. For 2000 mgkg: one rat showed loud breathing at 30 minutes control; other rat showed chromorrhinorrhea at 4 hours control; other rat showed moderate respiratory crackles in control 2 to 4 days after ingestion and mild respiratory crackles in controls 5 and 6 days after ingestion.
All the rats gained weight during the control time (14 days).
Necropsy of all the rats (dose 300 mg/kg bw and dose 2000 mg/kg bw): none gross pathology observations were detected. Any remaining protocol requised tissues, which have been examined, have no visible lesions.
Body weight:
All the animals gaines weight
Gross pathology:
None gross pathology observations were detected. Any remaining protocol requised tissues, which have been examinated, have no visible lesions.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Group A and Group B were treated with a dose level of 300 mg/kg and none of the treated animals shown a
test item-related mortatily.
In standard conditions a next group with 3 more animals would be treated at the maximum dose level, 2000
mg/kg, according to the OECD Guideline 423, but due to problems with the insolubility of the test item at the
maximum dose level it was not possible to check the mortality of a third group at 2000 mg/kg.
Therefore, it can be concluded that, according to the results obtained in this study and under the assayed
experimental conditions, the test item could be ranked in the Category 4 (LD50 cut-off value of 300 < LD50
< 2000 mg/kg of body weight), of the Globally Harmonised Classification System for Chemical Substances
and Mixtures.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
300 mg/kg bw
Quality of whole database:
The objective of this study is to evaluate the acute oral toxicity of the test item in female Sprague-Dawley rats by the Acute Toxic Class Method (OECD guideline Nº 423). The dose level to be used as the starting dose will be 300 mg/kg body weight, since the Sponsor has no information on the toxicity of the test item.
This method allows the test item to be classified according to the Globally Harmonised System (GHS) for the determination of the toxicity of chemicals.

The limit test is based on a stepwise procedure at one dose level of 300 mg/kg, which is carried out with six animals in two steps (three animals per step). The follow up doses were selected according the following scheme. After an observation period, test item-related mortality of the animals dosed at one step determined the next one. The time interval between doses was determined by the onset, duration, and severity of toxic signs. Animal treatment at the next dose was delayed until survival rate of previously dosed animals was determined.

Additional information

Clinical observations in response to treatment were performed 30 minutes, 2h, and 4h post-administration and once daily thereafter during the 14-day observation period.
Any visible clinical signs, discomfort and mortality were recorded. Clinical signs included changes in skin, fur, eyes and mucous membranes. Alterations in respiratory pattern, behaviour, posture, response to handling and the presence of abnormal movements were reported as well. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
No mortality was recorded.

Justification for classification or non-classification

It can be concluded that, according to the results obtained in this study and under the assayed experimental conditions, the test item could be ranked in the Category 4 (LD50 cut-off value of 300 < LD50 < 2000 mg/kg of body weight), of the Globally Harmonised Classification System for Chemical Substances and Mixtures.

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