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Description of key information

As no mortality was recorded in the present study at a dose of 2000 mg/kg b.w., the LD50 cut-off was set at >5000 mg/kg b.w for acute oral toxicity.

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:
27.04.2018 to 24.07.2018
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)
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:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
WISTAR Crl: WI(Han) rats
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-10 weeks
- Weight at study initiation: Step 1: 139–146 g; Step 2: 146–167 g
- Housing: Full barrier in an air-conditioned room
- Diet (e.g. ad libitum): yes
- Water (e.g. ad libitum): yes
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): 12h dark/ 12h light


Two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral
gavage administration at a dosage of 2000 mg/kg body weight. The test item was dissolved with the
vehicle aqua (sterile water) at a concentration of 0.2 g/mL and administered at a dose
volume of 10 mL/kg.
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
aqua (sterile water)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/ml
- Amount of vehicle (if gavage): 10ml/kg bw
- Justification for choice of vehicle: non-toxic characteristics.
- Lot/batch no. (if required): 705820
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 per step / 2 steps performed
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: All animals were observed for 14 days after dosing
- Frequency of weighing: on day 1 (prior to the administration) and on days 8 and 15 where day 1 is defined as the day of administration
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, morbidity and mortality, body weight, gross pathology
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
other: minor signs of toxicity with slight piloerection within 4 hours after application. One animal continued to show slight piloerection on the day after application and recovered within 2 days post-dose.
Gross pathology:
no findings
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present study, a single oral application of the test item TMA-TEMPO to
rats at a dose of 2000 mg/kg body weight was not associated with signs of toxicity or mortality.
The median lethal dose of TMA-TEMPO after a single oral administration to female rats, observed
over a period of 14 days is:
LD50 cut-off (rat): >5000 mg/ kg bw
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Under the conditions of the present study, a single oral application of the test item TMA-TEMPO to rats at a dose of 2000 mg/kg body weight was associated with slight signs of toxicity but no mortality. All animals survived until the end of the study showing minor signs of toxicity with slight piloerection within 4 hours after application. One animal continued to show slight piloerection on the day after application and recovered within 2 days post-dose. Throughout the 14-day observation period, the weight gain of the animals was within the normal range of variation for this strain. At necropsy, no macroscopic findings were observed in any animal of any step.

The study was conducted according to OECD TG 423, EC 440/2008 Method B.1 tris and OPPTS 870.1100.

The median lethal dose of TMA-TEMPO after a single oral administration to female rats, observed over a period of 14 days is:

LD50 cut-off (rat): >5000 mg/ kg bw

Justification for classification or non-classification

Based on the LD50 (rat): >2000 mg/ kg b.w. TMA-TEMPO is not classified for acute oral toxicity according to CLP Regulation (EC) No. 1272/2008.

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