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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018

Materials and methods

Test guidelineopen allclose all
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

Test material

Constituent 1
Chemical structure
Reference substance name:
[2,2,6,6-tetramethyl-4-(trimethylazaniumyl)piperidin-1-yl]oxidanyl chloride
EC Number:
814-375-0
Cas Number:
67036-09-3
Molecular formula:
C12H26N2OCl
IUPAC Name:
[2,2,6,6-tetramethyl-4-(trimethylazaniumyl)piperidin-1-yl]oxidanyl chloride
Test material form:
solid

Test animals

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.

Administration / exposure

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

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
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.
Body weight:
weight gain of the animals was within the normal range of variation for this strain
Gross pathology:
no findings

Applicant's summary and conclusion

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