N,N'-bis(2,2,6,6-tetramethylpiperidin-4-yl)hexane-1,6-diamine

Endpoint summary

Description of key information

Oral: LD50 (rat) = 820 mg/kg bw

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:

20 Dec 1984 - 22 Jan 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted May 12, 1981

Deviations:

no

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann, D-4799 Borchen
- Weight at study initiation: males: 172 g; females: 130 g
- Fasting period before study: 16 hours
- Housing: 1-5 animals in type III Makrolon
- Diet (ad libitum): R10 complete feed for rats, Ssniff Spezialfutter GmbH, D-4770 Soest
- Water (ad libitum): tap water
- Acclimation period: 4-8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

maize oil

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 cm³/kg bw

DOSAGE PREPARATION: The product was dissolved in maize germ oil at approximately 60 °C and administered at 40 °C.

Doses:

501, 631, 794, 1000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: before the treatment and 1, 7, 14 days after the treatment
- Necropsy of survivors performed: yes: All of the animals sacrificed at the end of the investigation and animals which died during the study period were dissected and macroscopically examined, and the findings were recorded.
- Other examinations performed: clinical signs: Up to six hours after the treatment and then daily, the onset, type and duration of all signs of toxicity and the time of death were noted.

Statistics:

The means (x) of the bodyweights were calculated. The LD50 is generally determined as described by Litchfield and Wilcoxon and reported with 95% confidence limits (J. Pharmacol. Exp. Ther. 96, 1949, 99).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

820 mg/kg bw

Based on:

test mat.

95% CL:

703 - 956

Mortality:

see Tab.1 (Any other information on results incl. tables)

Clinical signs:

other: Symptoms which occurred from approximately 30 minutes after administration were ruffled fur, in some case prone position, staggering, twitching, mild to strong sedation and ataxia, dark eyes and tremor and later crouched posture, hypothermia and, at the h

Gross pathology:

In the post-mortem dissections, hyperaemia of the gastric mucosa and small intestine mucosa, stasis of the liver and dark-coloured liver were observed. Dissection at the end of the test revealed in some animals hyperaemia of the gastric mucosa and small intestine mucosa, spots on both kidneys in 2 animals and in 2 animals only on the right kidney.

Tab.1 Acute oral toxicity (LD50) for rats

Dose mg/kg	Sex	Toxicological result	Death occurred within (h)	LD50 mg/kg
501	male	0/5/5 *
	female	0/5/5	-
631	male	2/5/5
	female	0/5/5	4
794	male	4/5/5		820 (703-956) slope function S = 1.36
	female	2/5/5	24
1000	male	3/5/5
	female	3/5/5	24

*number of animals which died/number of animals with signs/number of animals used

 

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

In the determination of the acute oral toxicity on male and female rats it was found that the LD50 of the test substance is 820 mg/kg bw. Under the experimental conditions described, the test substance fulfils the GHS criteria for classification into the acute toxicity Category IV.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

820 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral

The acute oral toxicity of the test substance was investigated in a study carried out according to OECD Guideline 401 (no information on GLP compliance given). The test substance (dissolved in maize oil) was administered by gavage to groups of 5 male and 5 female Wistar rats at 501, 631, 794 and 1000 mg/kg bw. Mortalities occurred at 631 mg/kg bw (2/5 males) within 4 h, and at 794 mg/kg bw (4/5 males, 2/5 females) and 1000 mg/kg bw (3/5 males, 3/5 females) within 24 h. Clinical signs were observed in all animals and occurred from approximately 30 min after administration. Symptoms included ruffled fur, in some case prone position, staggering, twitching, mild to strong sedation and ataxia, dark eyes and tremor and later crouched posture, hypothermia and, at the highest dose, in some cases paralysis of the rear legs. After 48 hours, all surviving animals were free of symptoms. In the post-mortem dissections, hyperaemia of the gastric mucosa and small intestine mucosa, stasis of the liver and dark-coloured liver were observed. Dissection at the end of the test revealed in some animals hyperaemia of the gastric mucosa and small intestine mucosa, spots on both kidneys in 2 animals and in 2 animals only on the right kidney.

The oral LD50 value for both male and females rats was determined to be 820 mg/kg bw (Study director 1985a).

In an earlier study, the test substance was administered as an aqueous solution (250 mg/mL, pH 11) to groups of 5 male and 5 female Wistar rats by gavage at 500, 630, 790, 1000 1260 and 1590 mg/kg bw. Mortalities occurred within 24 hours after administration at 630 mg/kg bw and above. At 500 mg/kg bw, animals showed a decreased motor activity, coordination disturbance, decreased motor activity, coordination disturbance, decreased reflex excitability, decreased grip- and limb tone and piloerection. These symptoms were present in the other groups (630-1590 mg/kg bw) at a higher degree. Furthermore, at higher doses the animals showed ptosis, cyanosis and tremor. The described toxicological symptoms appeared within 7 min after application and most of them persisted for 1 h and in some cases for 24 hours.Thereafter, all surviving animals showed a normal behaviour. The oral LD50 value for both male and females rats was determined to be 880 mg/kg bw (Ciba-Geigy Ltd. 1976).

Dermal and inhalation

There are no studies available on the acute toxicity of the test substance via the dermal or inhalation route. Due to its corrosive properties, acute toxicity studies do not generally need to be conducted according to Column 2, Section 8.5., of Annex VIII to the REACh Regulation (EC No. 1907/2006).

Justification for selection of acute toxicity – oral endpoint
The most criticial valid study data was selected.

Justification for classification or non-classification

Based on the available data on the acute oral toxicity, the test substance is harmful if swallowed and fulfils the criteria for classification according to DSD (67/548/EEC) and GHS (CLP, 1272/2008/EC).

DSD: R22

GHS: Acute toxicity - oral, Category 4