2,2,6,6-Tetramethylpiperidin-4-yl dodecanoate

Endpoint summary

Description of key information

Acute Toxicity:
- oral: 2/6 rats died at 2000 mg/kg bw (BASF SE, 10A0731/11X589, 2013)
- dermal: LD50 > 2000 mg/kg bw (rat, BASF SE, 11A0731/11X590, 2013)

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 and OECD guideline compliant study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

(December 17, 2001)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

(Bioassay, Labor für biologische Analytik GmbH, Heidelberg)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: approx. 10 – 11 weeks
- Weight at study initiation: mean weight test group 1: 168.7 +/- 3.51; mean weight test group 2: 179 +/- 1.00;
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: single housing in Makrolon cages, type III
- Diet: VRF1(P); SDS Special Diets Services, Altrip, Germany
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30 – 70%
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.24 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation. Additionally, at day of death in animals that died or were sacrificed moribund starting with study day 1. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals. A check for any dead or moribund animals was made at least once each workday.
- Necropsy of survivors performed: yes

Statistics:

Calculations were performed using Microsoft Excel 2003 and checked with a calculator.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 2/6 animals died

Mortality:

One animal of the first 2000 mg/kg bw test group was found dead in the cage on study day 2 and one animal of the second 2000 mg/kg bw test group was sacrificed in a moribund state on study day 3.

Clinical signs:

other: Clinical signs in the first 2000 mg/kg bw test group revealed in two out of three animals impaired general state and piloerection from study day 1 until study day 6 after administration. In one of these animals dyspnoea and reduced defecation were observe

Gross pathology:

The following macroscopic pathologic findings were observed in the animal that died (test group 1):
· Extensive haemorrhage of the glandular stomach
· Red discoloration and reddish content of the small intestine.
· Congestion of the kidneys

The following macroscopic pathologic finding was observed in the animal which was sacrificed in a moribund state (test group 2):
· Red discoloration of the small intestine.

There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and OECD guideline compliant study

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and OECD guideline compliant study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(February 24, 1987)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

(Bioassay Labor für biologische Analytik,GmbH, Heidelberg)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: male animals approx.8 weeks, female animals approx. 12 weeks
- Weight at study initiation:
- Fasting period before study:
- Housing: single housing in Makrolon cages, type III
- Diet: VRF1(P); SDS Special Diets Services, Altrip, Germany
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30 – 70%
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: clipped epidermis (dorsal and dorsolateral parts of the trunk)
- % coverage: at least 10% of the body surface
- Type of wrap if used: The test item was covered with an air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes (with warm water)
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.24 mL/kg bw

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of
observation. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals. Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter and on the last day of observation. A check for any dead or moribund animals was made at least once each workday.
- Necropsy of survivors performed: yes

Statistics:

Calculations were performed using Microsoft Excel 2003 and checked with a calculator.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality and no adverse findings upon necropsy occurred. Local irritation was observed.

Mortality:

No mortality occurred.

Clinical signs:

other: No systemic clinical signs were observed during clinical examination. Skin effects at the application site comprised well-defined erythema (grade 2) in all male animals 1 day after application which persisted in one animal until study day 2. This animal s

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Table 1: BODY WEIGHTS
Dose (mg/kg bw):	2000
Sex:	male
Administration:	1
Animal No.:	1	2	3	4	5	Mean weight	Standard deviation
Body weight at study day (g):
0	245	238	225	240	238	237,2	7,4
7	256	257	241	272	256	256,4	10,97
14	292	283	265	300	290	286	13,21
Dose (mg/kg bw):	2000
Sex:	female
Administration:	1
Animal No.:	1	2	3	4	5	Mean weight	Standard deviation
Body weight at study day (g):
0	210	200	204	206	201	204,2	4,02
7	212	200	209	205	197	204,6	6,19
14	228	209	216	213	203	213,8	9,31

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP and OECD guideline compliant study

Additional information

Oral:

In a GLP conform acute oral toxicity study conducted according to OECD 423 (BASF SE, 10A0731/11X589, 2013; reliability score 1) two groups of Wistar rats (2 x 3 female animals) were given a single oral dose (via gavage) of the test substance (unchanged, no vehicle) at a limit dose of 2000 mg/kg bw and observed for 14 days.

Oral LD50 (females) > 2000 mg/kg bw, expected to be less than 5000 mg/kg bw

One animal of the first 2000 mg/kg bw test group was found dead in the cage on study day 2 and one animal of the second 2000 mg/kg bw test group was sacrificed in a moribund state on study day 3. Clinical signs in the first 2000 mg/kg bw test group revealed in two out of three animals impaired general state and piloerection from study day 1 until study day 6 after administration. In one of these animals dyspnoea and reduced defecation were observed on study day 1 only and in the other animal on study day 1 and 2 after administration. In the third animal impaired general state, dyspnoea, piloerection and missing defecation was noted on study day 1 after administration (this animal was found dead in its cage on study day 2). The mean body weight of the surviving animals in the test groups increased throughout the study period within the normal range. The deceased animal (first group) and the animal, which was sacrificed in a moribund state (second group), lost body weight. The following macroscopic pathologic findings were observed in the animals that died: extensive haemorrhage of the glandular stomach, red discoloration and reddish content of the small intestine, congestion of the kidneys. There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.

 

Dermal:

In a GLP conform acute dermal toxicity study (BASF SE, 11A0731/11X590, 2013; reliability score 1) according to OECD 402 groups of Wistar rats (5 animals / sex) were dermally administered a limit dose of 2000 mg/kg bw of the test substance (unchanged, no vehicle) with a semiocclusive coverage for 24 h and observed for 14 days.

Dermal LD50(males/females) > 2000 mg/kg bw

No mortality occurred. No systemic clinical signs were observed during clinical examination. Skin effects at the application site comprised well-defined erythema (grade 2) in all male animals 1 day after application which persisted in one animal until study day 2. This animal showed moderate erythema (grade 3) on day 3. On study day 2, moderate erythema (grade 3) was observed in four male animals and persisted in 3 animals until day 3, in the fourth animal moderate erythema was observed until day 7. Thereafter well-defined erythema was noted in the animals until day 7, 8 or 9, respectively. Afterwards very slight erythema (grade 1) was observed until day 8, 10 or 13, respectively. Slight edema (grade 2) was noted in all male animals from study day 1 until study day 3 after application and persisted in two of these animals until study day 7. On study day 8 very slight edema (grade 1) was noted in these two animals. The other three animals showed very slight edema from study day 6 until study day 7, 8 or 9, respectively. Incrustations were observed in all male animals from study day 3 until day 10 or 13, respectively. In one animal plate-like incrustations were noted on study day 6 and 7. The mean body weights of the male animals increased within the normal range throughout the study period. The mean body weight of the female animals slightly increased or stagnated during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range. No macroscopic pathologic abnormalities were noted in the animals examined on the last day of observation.

Justification for selection of acute toxicity – oral endpoint
key study

Justification for selection of acute toxicity – dermal endpoint
key study

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. The LD50 values are above 2000 mg/kg bw. As a result the substance is not considered to be classified for acute oral and dermal toxicity under Directive 67/548/EEC, as amended for the 31st time in Directive 2009/2/EG.

 

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. The LD50 values are above 2000 mg/kg bw. As a result the substance is not considered to be classified for acute oral and dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the third time in Directive (EC 618/2012).

The substance requires classification for UN GHS acute class 5 for the oral route.