7-azatridecane-1,13-diamine

Endpoint summary

Description of key information

In a reliable skin irritation study in rabbits the submission substances induced scar formation and thus is assessed as corrosive to skin. In an eye irritation study similar to OECD TG 405 irreversible damage was observed when the submission substance was administered to the eyes of rabbits.

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:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given: comparable to guidelines /standards

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

prolonged exposure period, one additional animal; despite corrosiveness testing in all animals at the same time with long exposure period; additional application on scarified skin

Qualifier:

according to guideline

Guideline:

other: DRAIZE test published in "Appraisal of the safety of chemicals in foods and cosmetics" Association of Food and Drug Officials of the United States, published by the Editorial Committee, Baltimore (1959), p. 46

Deviations:

no

GLP compliance:

no

Remarks:

study performed before GLP statement

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.2 to 2.9 kg

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mg (solid test material humidified with a little bit of water)

Duration of treatment / exposure:

24 h

Observation period:

72 h

Number of animals:

4

Details on study design:

TEST SITE
- Area of exposure: two sites were shaved on the back of each animal, one of these was subsequntly sarified before the test item was applied


SCORING SYSTEM:
erythema scores similar to DRAIZE scoring system used in OECD 404
Erythema scores
0: none
1: very slight (barely perceptible)
2: slight (well perceptible)
3: moderate to severe
4: very severe erythema with slight eschar formation
8: very severe erythema and expanded eschar formation (over 50% of the apllication area)

Edema scores resemble those of OECD 404

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(for 4 tested animals)

Time point:

other: 24 h after start of exposure

Score:

2

Max. score:

8

Reversibility:

not reversible

Remarks:

within 72 hours

Remarks on result:

other: intact skin

Remarks:

all animals showed the same score

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(for 4 tested animals)

Time point:

other: 72 hours after start of exposure

Score:

8

Max. score:

8

Reversibility:

no data

Remarks:

on reversibility as this was the final period of time investigated in the study

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

mean

Remarks:

(for 4 tested animals)

Time point:

other: 24 hours after start of exposure

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72 hours

Remarks on result:

other: intact skin

Remarks:

all animals showed the same score

Irritation parameter:

edema score

Basis:

mean

Remarks:

(for 4 tested animals)

Time point:

other: 72 hours after start of exposure

Score:

4

Max. score:

4

Reversibility:

no data

Remarks:

on reversibility as this was the final period of time investigated in the study

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(for 4 tested animals)

Time point:

other: 24 after start of exposure

Score:

4

Max. score:

8

Reversibility:

not reversible

Remarks:

within 72 hours

Remarks on result:

other: scarified skin

Remarks:

individual scores: 8, 2, 4, 2

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(for 4 tested animals)

Time point:

other: 72 hours after start of exposure

Score:

8

Max. score:

8

Reversibility:

no data

Remarks:

on reversibility as this was the final period of time investigated in the study

Remarks on result:

other: scarified skin

Irritation parameter:

edema score

Basis:

mean

Remarks:

(for 4 tested animals)

Time point:

other: 24 hours after start of exposure

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72 hours

Remarks on result:

other: scarified skin

Remarks:

all animals showed the same score

Irritation parameter:

edema score

Basis:

mean

Remarks:

(for 4 tested animals)

Time point:

other: 72 hours after start of exposure

Score:

4

Max. score:

4

Reversibility:

no data

Remarks:

on reversibility as this was the final period of time investigated in the study

Remarks on result:

other: scarified skin

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Remarks:

study design does not allow to disciminate further into subcategories

Conclusions:

According to the authors of this study the test item was found to be extremely irritant to the skin of rabbits under the conditions tested.

Executive summary:

In order to test primary skin irritation 4 New Zealand White rabbits were treated the submission substance. 0.5 mg of solid test material (pasted with water) were applied onto the intact skin as well as on scarified skin of the animals and held in contact with skin for 24 h (occlusive conditions). Reading was performed 24 h and 72 h after start of the application. According to the authors of this study the test item was found to be extremely irritant to the skin of rabbits.

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:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given: comparable to guidelines /standards

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

: one additional animal

Qualifier:

according to guideline

Guideline:

other: DRAIZE test published in "Appraisal of the safety of chemicals in foods and cosmetics" Association of Food and Drug Officials of the United States, published by the Editorial Committee, Baltimore (1959), p. 46

Deviations:

no

GLP compliance:

no

Remarks:

study performed before GLP statement

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2 to 2.6 kg

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

Substance application was performed once, without any washing subsequently.

Observation period (in vivo):

7 days (Ocular reactions were observed at 1hour, 24, 48 and 72 hours after the instillation and then at days 7.)

Number of animals or in vitro replicates:

4

Details on study design:

SCORING SYSTEM: according to OECD TG 405 (Draize scale), reading at 1 h, 1, 2, 3, 4 and 7 days after removal of test item

The test item was instilled into the lower conjunctival sac of the left eye of each test animal.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days post application

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Remarks:

within 7 days post application

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

of animal #1, #2, and #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks:

within 7 days post application

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #4

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

not reversible

Remarks:

within 7 days post application

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days post application

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days post application

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3.33

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days post application

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3.33

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days post application

Irritant / corrosive response data:

Within 2 days post instillation the reading of all characteristics (i.e. corneal opacity, iris, conjunctivae redding, chemosis) in all animals resulted in maximum scores (see above), which were not reversible within 7 days post application.

Interpretation of results:

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

Conclusions:

Under the conditions tested the test item induced serious damage to eyes (corrosive).

Executive summary:

The primary eye irritation potential of the test item was investigated similar as described in OECD testing guideline no 405. The test item (0.1 g) was applied into the lower left conjunctival sac of the intact eye of four New Zealand White rabbits. Reading times were 1 h, 1, 2, 3, 4 and 7 days post instillation. Within 2 days post instillation the reading of all characteristics (i.e. corneal opacity, iris, conjunctivae redding, chemosis) in all animals resulted in maximum scores, which were not reversible within 7 days post application.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In order to test primary skin irritation 4 New Zealand White rabbits were treated the submission substance. 0.5 mg of solid test material (pasted with water) were applied onto the intact skin as well as on scarified skin of the animals and held in contact with skin for 24 h (occlusive conditions). Reading was performed 24 h and 72 h after start of the application. According to the authors of this study the test item was found to be extremely irritant to the skin of rabbits.

The primary eye irritation potential of the submission substance was investigated similar as described in OECD testing guideline no 405. The test item (0.1 g) was applied into the lower left conjunctival sac of the intact eye of four New Zealand White rabbits. Reading times were 1 h, 1, 2, 3, 4 and 7 days post instillation. Within 2 days post instillation the reading of all characteristics (i.e. corneal opacity, iris, conjunctivae redding, chemosis) in all animals resulted in maximum scores, which were not reversible within 7 days post application.

Justification for classification or non-classification

Based on the results of the reliable eye irritation study which is available for the submission substance and according to the criteria set in Regulation (EC) No. 1272/2008 the submission substance is classified for Irreversible effects on the eye/serious damage to eyes (Category 1).

Based on the results of the reliable skin irritation study and according to the criteria set in Regulation (EC) No. 1272/2008 section 3.2.2.6.1. the submission substance is identified as being corrosive to skin. However no definite subcategory with criteria described in Regulation (EC) No. 1272/2008 Table 3.2.1 could be chosen as the study design (exposure period 4 hours) did not allow for further discrimination, thus the strongest classification as Corrosive subcategories 1A was assigned.