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Diss Factsheets

Administrative data

Description of key information

Oral: LD50 > 2000 mg/kg bw and the LD50= LD50 cut-off was considered to be > 5000mg/kg bw female rat, OECD TG 423, 2019

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:
05-08-2019 to 12-11-2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Guideline study performed under GLP. All relevant validity criteria were met.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han) (outbred, SPF-Quality)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Rationale for alternative/additional species to rat: Not applicable.
- Source: Recognised supplier (documented in the full study report)
- Females (if applicable) nulliparous and non-pregnant: Yes.
- Rationale for use of males: Not applicable.
- Age at study initiation: 8 - 12 weeks (young adult, ca. 9 weeks)
- Weight at study initiation: 156 - 189 g (2000 mg/kg dose level) ; bodyweight variation did not exceed ±20% of the mean bodyweight at study initiation.
- Fasting period before study: Overnight before dosing and three to four hours after dosing.
- Housing: Group housed in groups of up to three in polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust as bedding material, paper environmental enrichment and equipped with water bottles.
- Historical data: The laboratory has a historic control dataset (not documented in the full study report).
- Diet (e.g. ad libitum): Certified diet from recognised supplier, provided ad libitum (except for fasting period).
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 5 days.
- Microbiological status when known: No issues reported within the study.
- Method of randomisation in assigning animals to test and control groups: Randomly allocated to cages after receipt.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 24 (actual mean = 21 °C)
- Humidity (%): 40 - 70% (actual 47% to 69%)
- Air changes (per hr): > 10 air changes per hour
- Photoperiod: 12 h light / 12 h dark

IN-LIFE DATES: From: 06-08-2019 to 22-11-2019
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Not applicable.
- Amount of vehicle (if gavage): Not applicable.
- Justification for choice of vehicle: Not applicable.
- Lot/batch no. (if required): Not applicable.
- Purity: Not applicable.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (2.23 mL/kg) body weight. Dose volume calculated as dose level (g/kg) / density (g/mL)

DOSAGE PREPARATION (if unusual): Not applicable.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of data suggesting the test item was toxic, 2000 mg/kg was chosen as the starting dose. The toxicity of the test item was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.
Doses:
2000 mg/kg
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Mortality/Viability: Twice daily; Bodyweights: Days 1 (pre-administration), 8 and 15; Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The signs were graded according to fixed scales and the time of onset, degree and duration were recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
2000 mg/kg bw : No mortality.
Clinical signs:
other: 2000 mg/kg bw : Hunched posture (6/6 females), uncoordinated movements (1/6 females) and piloerection (3/6 females) were noted between Days 1 and 3. (Max grade = 1). All effects fully reversed by Day 4.
Gross pathology:
2000 mg/kg bw : No abnormalities were noted at necropsy that was considered toxicologically relevant. The reddish, several/isolated foci of the thymus, found in three females (#2, #3 and #5) at macroscopic examination, are occasionally seen in rats of this age and strain and was therefore considered not toxicologically relevant.
Other findings:
- Organ weights: Not applicable.
- Histopathology: Not applicable.
- Potential target organs: Not applicable.
- Other observations: Not applicable.
Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the oral LD50 was established to exceed 2000 mg/kg bw in female Wistar rats. According to OECD TG 423 the LD50 cut-off value was considered to exceed 5000 mg/kg bw .
Executive summary:

The study was performed according to OECD TG 423 and EU Method B1 tris Acute Toxicity, US EPA OPPTS 870.1100 and Japanese JMAFF guidelines under GLP to assess the acute oral toxicity of the test item following a single oral administration in the female Wistar strain rat by the acute class method. The test item was administered by oral gavage to two individual groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred. Hunched posture (6/6 females), uncoordinated movements (1/6 females) and piloerection (3/6 females) were noted between Days 1 and 3 (maximum grade = 1). All effects fully reversed by Day 4. The mean body weight gain shown by the females over the study period was considered to be normal and similar to that expected for normal untreated animals of the same age and strain. No abnormalities were noted at necropsy that was considered toxicologically relevant. The oral LD50 value of the test item in Wistar rats was established to exceed 2000 mg/kg body weight. According to the OECD TG 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The available information as a whole meets the tonnage driven information requirements of REACH..

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

Key study : OECD TG 423, 2019 : The study was performed according to OECD TG 423 and EU Method B1 tris Acute Toxicity, US EPA OPPTS 870.1100 and Japanese JMAFF guidelines under GLP to assess the acute oral toxicity of the test item following a single oral administration in the female Wistar strain rat by the acute class method. The test item was administered by oral gavage to two individual groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred. Hunched posture (6/6 females), uncoordinated movements (1/6 females) and piloerection (3/6 females) were noted between Days 1 and 3 (maximum grade = 1). All effects fully reversed by Day 4. The mean body weight gain shown by the females over the study period was considered to be normal and similar to that expected for normal untreated animals of the same age and strain. No abnormalities were noted at necropsy that was considered toxicologically relevant. The oral LD50 value of the test item in Wistar rats was established to exceed 2000 mg/kg body weight. According to the OECD TG 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Justification for classification or non-classification

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity.