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

Endpoint summary

Description of key information

The test substance is corrosive to the skin and causes serious eye damage.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 Jan 1985 - 24 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 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted May 12, 1981

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

other: Kleinrussen Chbb-SPF

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Fa. Dr. Karl Thomae GmbH, Biberach
- Weight at study initiation: 2.1-2.5 kg
- Housing: individually in stainless steel cages
- Diet (ad libitum): K4 Alleindiät for rabbits, Ssniff Spezialfutter GmbH, 4770 Soest, ad libitum
- Water (ad libitum): tap water ad libitum
- Acclimation period: 14 days

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

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

other: paraffin oil for humidification

Controls:

other: the untreated sites of the same animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

6 (3 males and 3 females)

Details on study design:

TEST SITE
- Area of exposure: 6 cm²
- Type of wrap if used: polyethylene foil with an elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing: rinsed with warm water
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to Draize

Irritation parameter:

erythema score

Basis:

animal: #1-6

Time point:

other: mean over 24, 48, 72 hours

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal: #1-4

Time point:

other: mean over 24, 48, 72 hours

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: mean over 24, 48, 72 hours

Score:

3

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #6

Time point:

other: mean over 24, 48, 72 hours

Score:

3.7

Max. score:

4

Reversibility:

not reversible

Irritant / corrosive response data:

Test substance showed severe irritating effects on male and female rabbit skin. Necrosis (full thickness) appeared after 4 hours, but not after 3 minutes. See also Table 1 (Any other information on results)

Table 1. Evaluation of sin reactions, individual scores (Draize) and observations.

 

Animal #	Sex	Reading time point post-exposure
		1h		24 h		48 h		72 h
		Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
1	M	4 (1)	4	4 (1)	4	4 (2,3,4)	4	4 (1,4,5)	4
2	M	4 (1)	2	4 (1)	4	4 (1,3,4)	4	4 (1,5)	4
3	M	4 (1)	3	4 (1)	4	4 (1)	4	4 (1,5)	4
4	F	4 (1,2)	4	4 (1)	4	4 (1,3,4)	4	4 (1,4,5)	4
5	F	4 (1, 2)	3	4 (1)	2	4 (1,3,4)	4	4 (1,4,5)	4
6	F	4 (1)	4	4 (1)	4	4 (1)	4	4 (1,5)	3

 

1: Bloody necrosis and strong green colour

2: Necrosis, green colour at the edges of the application site

3: Application site hardened

4: Deep wounds

5: Scab

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Remarks:

Migrated information

Conclusions:

Under the experimental conditions described, the test substance fulfils the GHS criteria for classification as corrosive (Category 1C).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 Jan -15 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 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted May 12, 1981

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

other: Kleinrussen: Chbb-SPF

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Fa. Dr. Karl Thomae GmbH, Biberach
- Weight at study initiation: 2.09 kg (average)
- Housing: individually in stainless steel cages
- Diet (ad libitum): K4 Alleindiät for rabbits; Ssniff Spezialfutter GmbH, 4770 Soest, ad libitum
- Water (ad libitum): tap water ad libitum
- Acclimation period: 14 days

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

Vehicle:

unchanged (no vehicle)

Controls:

other: left eye of the same animal remained untreated and served as control

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

1 hour

Number of animals or in vitro replicates:

1

Details on study design:

SCORING SYSTEM: according to Draize

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 1 hour

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 1 hour

Score:

2

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

other: 1 hour

Score:

3

Max. score:

3

Reversibility:

not reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 1 hour

Score:

2

Max. score:

4

Reversibility:

not reversible

Irritant / corrosive response data:

Cornea: immediate opaqueness and hyperaemia of mucosa and nictitating membrane. 1 hour after the application mucosa and nictitating membrane were burned, bloody and dark to black coloured. The cornea was coloured pearl-green.
Iris: The iris could not be completely detected and showed no reaction to light.
Conjunctiva: Exudate was mixed with blood.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Remarks:

Migrated information

Conclusions:

Under the experimental conditions described, the test substance fulfils the GHS criteria for classification as eye irritant Category 1 (irreversible effects on the eye).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion

The skin irritation/corrosion potential of the test substance was assessed in a study performed in accordance to OECD guideline 404. The shaved skin of 3 male and 3 female Kleinrussen Chbb-SPF rabbits was exposed to 0.5 g of the test substance (in paraffin oil) for 4 hours under occlusive conditions. Thereafter, the test material was removed by washing with warm water. Skin reactions were assessed 1, 24, 48 and 72 hours after removal of the test substance. Test substance showed severe irritating effects on male and female rabbit skin. Necrosis (full thickness) appeared after 4 hours, but not after 3 minutes. The mean erythema score over 24, 48 and 72 h was 4.0 in all animals. The mean edema score over 24, 48 and 72 h was 4.0 in four animals and 3.0 and 3.7 in the remaining two animals, respectively. Due to severe skin effects, the study was terminated after 72 hours and animals were sacrificed (Study director 1985b).

In another study conducted according to EPA OPP 81-5, the test substance (0.5 g) was applied to both intact and abraded skin of 3 male and 3 female New Zealand White rabbits as a 50% solution in propylene glycol and saline (70:30). The skin was exposed to the test substance for 24 h under occlusive conditions. Skin reactions were assessed 24, 48 and 72 h and 4 and 7 days post-application. For the intact skin, the overall mean erythema score over 24, 48 and 72 h was 2.1 (mean score of 4/6 animals = 2, 1/6 animals = 3, 1/6 animals = 1.7). The overall mean edema score over 24, 48 and 72 h was 1.2 (mean individual scores: 0.7, 3.0, 0.3, 1.0, 2.0, 0.0). The observed effects were not fully reversible within the observation period of 7 days post-application. No further information on irritant/corrosive or other effects was reported (Ciba-Geigy Ltd. 1980a).

Eye irritation

The test substance was assessed for eye irritation/corrosion in one Kleinrussen Chbb-SPF rabbit in a study performed according to the OECD guideline 405. The test substance (0.1 g) was applied into the conjunctival sac of one eye; the other eye served as control. The test substance was not removed after application. Cornea effects included immediate opaqueness and hyperaemia of mucosa and nictitating membrane. One hour after the application, mucosa and nictitating membrane were burned, bloody and dark to black coloured. The cornea was coloured pearl-green. Due to cornea opaqueness, the iris could not be completely detected and showed no reaction to light. In the conjunctiva, exudate was mixed with blood. Due to the corrosive effects, the study was terminated 1 h post-application. At this time point, the treated eye was scored the maximum values for cornea (4), iris (2), conjunctivae (3) and chemosis (4) (Study director 1985c).

In another study conducted according to EPA OPP 81-4, the test substance was assessed for eye irritation in two groups of 3 New Zealand White rabbits. An amount of 0.1 g was applied into the conjunctival sac of one eye of all animals; the other eye served as control. The treated eyes of 3 animals were not rinsed. The treated eyes of the 3 other animals were rinsed with physiological saline ca. 30 sec post-application. Eye reactions were assessed 24, 48 and 72 h and 4 and 7 days post-application. For the treated eyes without rinsing, the overall mean cornea score over 24, 48 and 72 h was 3.2 (individual mean scores: 3.7, 4.0, 2.0). The overall mean iris score over 24, 48 and 72 h was 0.9 (individual mean scores: 1.0, 1.0, 0.7). The observed effects were not fully reversible within the observation period of 7 days post-application. No further information on irritant/corrosive or other effects was reported (Ciba-Geigy Ltd. 1980b).

Justification for selection of skin irritation / corrosion endpoint:
The most criticial valid study data was selected.

Justification for selection of eye irritation endpoint:
The most criticial valid study data was selected.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Based on the available data on skin irritation/corrosion and eye irritation, the test substance is corrosive to the skin and causes serious eye damage, and fulfils the criteria for classification according to DSD (67/548/EEC) and GHS (CLP, 1272/2008/EC).

DSD: R34

GHS: Skin Corrosive Category 1C, Eye Damage Category 1