2,2,6,6-tetramethylpiperidin-4-ol

Endpoint summary

Description of key information

oral: LD50 (female) = 1564 mg/kg bw (GLP-OECD Study, MHW, 1998)
         LD50 (male)    = 1482 mg/kg bw (GLP-OECD Study, MHW, 1998)
         LD 50 (female) = 2104 mg/kg bw (OECD Study, CIBA, 1983)
         LD50 (male)     = 2729 mg/kg bw (OECD Study, CIBA, 1983)
         LD50 (male/female) > 2000 mg/kg (OECD Study, Evonik, 1993)
Dermal: LD50 > 2000 mg/kg bw (GLP, OECD Study, CIBA, 1992)

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: Guideline study (OECD)

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Remarks:

Biosafety Research Center, Food, Drugs and Pesticides (An-Pyo Center), Japan

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7 weeks old
- Weight at study initiation: 177 - 195 g for males, 139 - 153 g for females

Route of administration:

oral: gavage

Vehicle:

water

Doses:

590, 769, 1000, 1300, 1690, 2197 mg/kg bw

No. of animals per sex per dose:

no data

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each rat was weighed immediatly prior to treatment, the day after and weekly thereafter for two-week post-treatment observation period. The rats were observed periodically.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Statistics:

Lichtfield-Wilcoxon method

Sex:

female

Dose descriptor:

LD50

Effect level:

1 564 mg/kg bw

95% CL:

1 326 - 1 842

Sex:

male

Dose descriptor:

LD50

Effect level:

1 482 mg/kg bw

95% CL:

1 239 - 1 774

Mortality:

Death of animals was observed at 1300 mg/kg and higher dose groups of the both sexes. No obvious sex difference was noted. At doses ≥ 1690 mg/kg, death occurred mostly on the day after dosing.

Clinical signs:

other: In all groups, clinical signs of decreased locomotor activity, mydriasis and blepharoptosis were observed in both sexes and were most pronounced at the highest dose applied (2197 mg/kg). Prone position, hypothermia and tremors were observed in 1300 mg/kg

Gross pathology:

Pathological examinations were conducted in rats which died prematurely. Pathological lesions due to 2,2,6,6-Tetramethylpiperidin-4-ol were observed in the stomach and duodenum of both sexes, consisting of haemorrhages, necrosis, and vacuolar degeneration (stomach and duodenum) and edema (duodenum).

Mortality of male and female rats dosed orally with the undiluted test material:

dose level (mg/kg)	#dead/#treated		Time of Death
	Males	Females	Males	Females
592	0/5	0/5	-	-
769	0/5	0/5	-	-
1000	0/5	0/5	-	-
1300	1/5	1/5	1 rat - day 13	1 rat - day 6
1690	4/5	3/5	3 rats - day 1	3 rats - day 1
			1 rat - day 7
2197	5/5	5/6	5 rats - day 1	5 rats - day 1

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: Guideline study (OECD)

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Remarks:

Short-term Toxicology, CIBA-GEIGY Limited

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tif: RAI f1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production 4332 Stein / Switzerland
- Weight at study initiation: 219 to 252 g
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- % coverage: at least 10% of the body surface

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 ml/kg
- Constant volume or concentration used: no

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: daily; weighing: immediately before application and on days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Lichtfield-Wilcoxon method

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortalities occurred in this study.

Clinical signs:

other: Piloerection and hunched posture were seen, which are considered as common and unspecific symptoms in acute dermal tests due to treatment. At the application site erythema were seen in all animals. Necrosis was observed in one male and one female. The ani

Gross pathology:

At necropsy, no abnormalities were found.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Additional information

Oral: The study performed by MHW (Japan, 1998) was identified as the key study because they were well conducted and described in detail.

1. MHW study: Male and female Crj :CD (SD) rats were administered orally with 2,2,6,6 -tetramethylpiperidin-4 -ol at doses of 590, 769, 1000, 1300, 1690 and 2197 mg/kg and observed for two weeks. In all groups, clinical signs of decreased locomotor activity, mydriasis and blepharoptosis were observed in both sexes. Prone position, hypothermia and tremors were observed at 1300 mg/kg or higher doses in both sexes. Moreover, wasting, abdominal distension and pallor of the auricles at 1300 mg/kg and piloerection in the males at 1690 mg/kg, as well as abdominal distension, pallor of auricles and loss of fur in the females at 1690 mg/kg were observed. Pathological examination was conducted in the male and female rats which died, hemorrage, necrosis, and vacuolar degeneration were seen in the stomach gland, and edema, hemorrhage, necrosis and vacuolar degeneration were observed in the duodenum. LD50 was established at 1482 mg/kg for male and 1564 mg/kg for female rats, respectively.

2. Ciba study: Single doses of 1000, 2000, 3500, 5000 mg/kg bw were administered and followed by a 14 day post-treatment observation period. The following LD50 was determined for 2,2,6,6 -tetramethylpiperidin-4 -ol: LD50 (female) = 2404 mg/kg bw., LD50 (male) = 2729 mg/kg bw, the average LD50 (male/female) = 2413 mg/kg bw. Dyspnoea, ruffled fur and curved body position were seen, being common symptoms in acute tests. In the doses of 2000 mg/kg and higher sedation was observed. Tremor and tonic clonic convulsions were noted once in the two high dose groups.

Conclusion: 2,2,6,6 -tetramethylpiperidin-4 -ol shows slight acute toxicity when administered orally to the albino rat.

Dermal: Dermal acute toxicity study of rat was conducted in a OECD guideline study by CIBA (1992) at a dose of 2000 mg/kg only. Piloerection and hunched posture were seen, being common symptoms in both sexes. At the application site erythema was seen in all animals. Necrosis was observed in one male and one female. The animals recovered within 8 to 13 days. Death of rats was not observed during the examination. The LD50 was higher than 2000 mg/kg bw for both sexes.

Conclusion: 2,2,6,6 -tetramethylpiperidin-4 -ol shows no acute toxicity when administered dermal to the albino rat.

Inhalation: no data available.

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. As slight acute toxicity were observed when administered orally, 2,2,6,6 -tetramethylpiperidin-4 -ol has to be classified as Category 4 (H302). 

Based on the data for dermal toxicity, classification is not warranted under Regulation (EC) No.1272/2008.