[2,2,6,6-tetramethyl-4-(trimethylazaniumyl)piperidin-1-yl]oxidanyl chloride

Endpoint summary

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.