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Administrative data

Description of key information

The available data indicate a potential for acute toxicity. The acute oral toxicity (LD50) in rats was determined to be larger than 300 mg/kg and smaller than 2000 mg/kg bw, a cut-off of 500 mg/kg bw was derived (Evonik, 2003, OECD 423). The acute dermal lethal dose (LD50) of the test item N-Butyl-TAD was found to be lower than 2000 mg/kg bw in male and female CRL:(WI) rats in a limit test. Due to the corrosive potential of the test item, a full test was not performed for animal welfare reasons.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
RTC, Rome, Italy
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Italy, San Pietro al Natisone (UD), Italy
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 176-200 g
- Fasting period before study: overnight before dosing
- Housing: 3 animals per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days prior dosing


ENVIRONMENTAL CONDITIONS
according to guideline
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 and 30 mg/mL
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: soluble in water

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg
Doses:
2000 and 300 mg/kg bw.
No. of animals per sex per dose:
3 (300 mg/kg bw was dosed in two steps with 3 animals each)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality/morbidity: twice daily; observations: 30 min, 1 (except step 2 and 3), 2 and 4 h post application and daily thereafter; weighing immediately prior dosing, days 2, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 cut-off
Mortality:
2000 mg/kg bw: all animals died within 4 hours post application
300 mg/kg bw: no mortality in two groups of 3 females each
Clinical signs:
Reduced activity, hunched posture, lethargy semi to full closed eyes, piloerection, salivation and mucus in the litter tray, recovery occurred by day 2 at 300 mg/kg bw.
Body weight:
within the normal range
Gross pathology:
no abnormalities were observed in any animal at the necropsy examination

According to Annex 2d of OECD TG 423 an LD50 cut-off of 500 mg/kg bw could be derived.

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under conditions tested, all animals died on the day of dosing at a dose level of 2000 mg/kg bw. At a dose level of 300 mg/kg bw, no mortality was observed. Main clinical findings were reduced activity, hunched posture, lethargy semi to full closed eyes, piloerection, salivation and mucus in the litter tray, recovery occurred by day 2 at 300 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
500 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30.01.2015 to 30.10.2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: CRL:(WI) rats
- Weight at study initiation: males 226-243 g, females 209-247 g
- Housing: individual caging in Type II cages (polypropylene/polycarbonate)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.9-24.8
- Humidity (%): 37-50
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The back of each animal was shaved (approximately 10 % area of the total body surface) approximately 24 hours prior to treatment. The test item was applied as a single dose as supplied to the shaved skin and remained in contact with the skin for the 24-hour exposure period. Sterile gauze pads were placed on the skin of rats to cover the test item. These gauze pads were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi-occlusive plastic wrap for 24 hours.
Duration of exposure:
24h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 male
5 female
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
< 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Administration of the test item led to the death of 10/10 animals at the dose level of 2000 mg/kg bw. Seven out of ten animals were found dead, and 3/10 animals were in moribund status at the observation 24 hours post application. Moribund animals were euthanized for animal welfare reason after consultation with the Clinical Veterinary.
Clinical signs:
At 5 hours post application, animals were symptom free. At 24 hours post application, 4 male, 3 female animals were found dead and 1 male, 2 female animals were in a moribund status (verified by the Clinical Veterinary).
During the assessment of the general distress of moribund animals by the Clinical Veterinary, it was found that the moribund eyes of the animals were half closed, natural behaviour become very still or not alert, hydration status of turgor of skin decrease. Moreover decreased respiration rate with abdominal breathing and very weak or lying on cage floor without response were noticed.
Body weight:
Males: 202-217 g
Females: 196-225 g
The animals lost the 6-12% of the starting body weight during 24 hours.
Gross pathology:
A single 24-hour dermal application of N-Butyl-TAD to CRL:(WI) rats at a dose level of 2000 mg/kg bw led to the preterminal euthanasia (three rats) or death (seven rats) on Day 1. Test item-related black diffuse discoloration of the skin (external examination) and red-black diffuse discoloration of the skin (internal examination) were observed at the sites of application. Dark/red discoloration of the collapsed/non-collapsed lungs were typical for found dead animals.
Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The application of the test item at 2000 mg/kg bw caused extremely severe local dermal signs and led to the death of 10/10 animals (7 dead, 3 euthanized). The acute dermal median lethal dose (LD50) of the test item N-Butyl-TAD was found to be lower than 2000 mg/kg bw in male and female CRL:(WI) rats in a limit test. Due to the corrosive potential of the test item, a full test was not performed for animal welfare reasons.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

The acute oral toxicity of N-Butyl-2,2,6,6-tetramethylpiperidine-4-amine was investigated following administration of a single dose to the rat by gavage. A single group of 3 female animals was dosed at a level of 2000 mg/kg. All animals died within 4 hours of dosing. Reduced activity, hunched posture, lethargy and closed eyes were observed prior to death. An additional group of 3 female animals was then dosed at 300 mg/kg and observed for a period of 14 days. No mortality occurred. Clinical signs included piloerection, reduced activity, hunched posture and semi-closed eyes, which were observed on the day of dosing. Recovery had occurred by Day 2. A group of 3 female animals was subsequently dosed at the same level (300 mg/kg) with the same result. Changes in body weight observed in treated animals were not remarkable. A reduced body weight gain or a body weight loss was noted at the end of the first week of the study, but recovery was observed at the end of the study. No abnormalities were observed in any animal at necropsy examination.

The LD50 is greater than 300 mg/kg, but less than 2000 mg/kg body weight. According to OECD TG 423 an LD50 cut off value of 500 mg/kg body weight can be derived from these results.

An acute dermal toxicity study was performed with test item N-Butyl-TAD in CRL:(WI) rats, in compliance with OECD TG 402. A limit test was carried out at 2000 mg/kg bw in both sexes (5 rats/sex). The test item was applied as supplied as a single dermal 24-hour exposure followed by a 24 hour observation period. At 5 hours post application, animals were symptom free. At 24 hours post application, 4 male, 3 female animals were found dead and 1 male, 2 female animals were in a moribund status and euthanized for animal welfare reason after consultation with the Clinical Veterinary. It was found that the moribund eyes of the animals were half closed, natural behaviour become very still or not alert, hydration status of turgor of skin decrease. Moreover decreased respiration rate with abdominal breathing and very weak or lying on cage floor without response were noticed. Test item-related black diffuse discoloration of the skin (external examination) and red-black diffuse discoloration of the skin (internal examination) were observed at the sites of application. Dark/red discoloration of the collapsed/non-collapsed lungs were typical for found dead animals.

The acute dermal lethal dose (LD50) of the test item N-Butyl-TAD was found to be lower than 2000 mg/kg bw in male and female CRL:(WI) rats in a limit test. Due to the corrosive potential of the test item, a full test was not performed for animal welfare reasons.


Justification for selection of acute toxicity – oral endpoint
There is one fully valid acute oral toxicity study available.

Justification for selection of acute toxicity – dermal endpoint
There is one fully valid acute dermal toxicity study available.

Justification for classification or non-classification

The acute oral lethal dose (LD50) in rats was determined to be larger than 300 mg/kg and smaller than 2000 mg/kg bw, a cut-off of 500 mg/kg bw was derived.

The test substance is classified for this endpoint in accordance to the CLP Regulation (EC) No 1272/2008 with acute oral toxicity category 4.

The acute dermal lethal dose (LD50) of N-Butyl-TAD was found to be lower than 2000 mg/kg bw in male and female CRL:(WI) rats in a limit test. Due to the corrosive potential of the test item, a full test was not performed for animal welfare reasons.

The test substance is classified for this endpoint in accordance to the CLP Regulation (EC) No 1272/2008 with acute dermal toxicity category 4.