3-[[3-(dimethylamino)propyl]amino]propiononitrile

Endpoint summary

Description of key information

The skin and eye irritation was determined by studies using methods available before the publication of OECD guidelines. The methods used however, are equivalent to modern guidelines.

Using these methods and based on the results obtained, Aradur 1019 is determined to be a moderate skin irritant and a severe eye irritant.

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:

January 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

The test was performed on 3 male and 3 female rabbits of the Himalayan breed weighing 1.5 to 2 kg. They were housed individually in metal cages, were kept at a constant room temperature of 22 + 1° C, at a relative humidity of 55 + 5 % and on a 10 hours light cycle day. The animals received ad libitum Standard rabbit food - NAFAG, Gossau SG - and water. Prior to treatment,they were adapted to our laboratories for a minimum of 4 days.

Type of coverage:

occlusive

Preparation of test site:

other: Shaved. Left side slightly scarified.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5ml of test material was applied

Duration of treatment / exposure:

Dressings were removed after after 24 hours exposure

Observation period:

Observations were made 24 and 72 hours after application of test material

Number of animals:

6 animals, 3 male and 3 female

Irritation parameter:

erythema score

Basis:

mean

Remarks:

Intact skin

Time point:

24 h

Score:

2.3

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

Scarified skin

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

Intact skin

Time point:

72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

Scarified skin

Time point:

72 h

Score:

3.8

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

Intact skin

Time point:

24 h

Score:

2.2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

Scarified skin

Time point:

24 h

Score:

2.2

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

Intact skin

Time point:

72 h

Score:

0.5

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

Scarified skin

Time point:

72 h

Score:

2.8

Max. score:

4

Reversibility:

not fully reversible within: 72 h

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

intact skin

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

not fully reversible within: 72h

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.1

Max. score:

4

Reversibility:

not fully reversible within: 72h

Remarks on result:

positive indication of irritation

Animal No. Sex	Skin Reaction	24 hours after application		72 hours after application
		Intact skin	Scarified skin	Intact skin	Scarified skin
1 ♂	Erythema	2	4	2	4
	Edema	2	2	0	1
2 ♂	Erythema	2	4	2	3
	Edema	2	2	0	13
3 ♂	Erythema	2	4	3	4
	Edema	2	2	0	0
4 ♀	Erythema	2	4	4	4
	Edema	3	3	1	1
5 ♀	Erythema	4	4	4	4
	Edema	2	2	1	1
6 ♀	Erythema	2	4	3	4
	Edema	2	2	1	1

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The primary irritation index, a measure of the acute irritation to the rabbit skin was 4.7. This indicates that the test material is a moderate irritant to the rabbit skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

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:

January 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

The study report calculates scores based on grading of ocular lesions that are similar or equivalent (in many cases identical) as those described in Table 1 of OECD test guideline 405 (2nd Oct 2012). The study however, uses the initial figure to calculate a final score out of 80 for cornea, 10 for iris and 20 for conjunctivae.
Based on the calculation given, and that the results for unrinsed eyes are all maximum scores and irreversible, it is easy to adapt the give scores of 80, 10 and 20 to the modern maximum scores of 4, 2 and 3.

GLP compliance:

no

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

The animals were housed individually in metal cages, were kept at a constant room temperature of 22 + 1 C, at a relative humidity of 55 + 5 % and on a 10 hour light cycle day. The animals had ad libitum access to Standard rabbit food - NAFAG, Gossau SG - and water. Prior to treatment they were adapted to our laboratories for a minimum of 4 days. Only rabbits with normal ophthalmic findings were used for these tests.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1ml of the test material was inserted into the conjunctival sac of the left eye

Duration of treatment / exposure:

Eyelids were gently closed for on second.
In 3 of the 6 rabbits approximately 30 seconds after treatment the treated eye was flushed with 10 ml of lukewarm water.

Observation period (in vivo):

7 days.
Eye irritation was appraised with a slit-lamp on day 1, 2, 3, 4 and 7

Number of animals or in vitro replicates:

6 rabbits

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

Unrinsed eyes

Time point:

24/48/72 h

Score:

80

Max. score:

80

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Remarks:

Because of irreversible maximum irritation effect all rabbits were kill after an observation period of 72 hours.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

Eyes rinsed after 30 seconds

Time point:

7 d

Score:

41.3

Max. score:

80

Reversibility:

not fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

Unwashed eyes

Time point:

7 d

Score:

20

Max. score:

20

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

Eyes rinsed 30 seconds after treatment

Time point:

7 d

Score:

3.7

Max. score:

10

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

Unwashed eyes

Time point:

7 d

Score:

20

Max. score:

20

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

Eyes rinsed 30 seconds after treatment

Time point:

7 d

Score:

12.3

Max. score:

20

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

with eyes rinsed 30 sec. after treatment

Time point:

24/48/72 h

Score:

42.2

Max. score:

60

Reversibility:

not fully reversible within: 72h

Irritation parameter:

iris score

Basis:

mean

Remarks:

with eyes not rinsed after treatment

Time point:

24/48/72 h

Score:

10

Max. score:

10

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Remarks:

Because of irreversible maximum irritation effect all rabbits were kill after an observation period of 72 hours.

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

with eyes not rinsed after treatment

Time point:

24/48/72 h

Score:

20

Max. score:

20

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Remarks:

Because of irreversible maximum irritation effect all rabbits were kill after an observation period of 72 hours.

Irritation parameter:

chemosis score

Remarks:

with eyes not rinsed after treatment

Basis:

mean

Time point:

24/48/72 h

Score:

20

Max. score:

20

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Eye irritation in individual rabbits with eyes not rinsed after treatment:

	Rabbit 1 ♂			Rabbit 2 ♂			Rabbit 3 ♂
Days after Application	Cornea	Iris	Conjunctivae	Cornea	Iris	Conjunctivae	Cornea	Iris	Conjunctivae
1	80	10	20	80	10	20	80	10	20
2	80	10	20	80	10	20	80	10	20
3	80	10	20	80	10	20	80	10	20
4	Because of the irreversible maximum irritation effect, all rabbits were killed after an observation period of 72 hours
7

Eye irritation in individual rabbits with eyes rinsed 30 sec. after treatment:

	Rabbit 4 ♀			Rabbit 5 ♀			Rabbit 6 ♀
Days after Application	Cornea	Iris	Conjunctivae	Cornea	Iris	Conjunctivae	Cornea	Iris	Conjunctivae
1	40	0	10	40	5	14	60	10	16
2	30	0	10	30	0	12	60	10	16
3	30	0	10	30	0	12	60	10	16
4	30	0	8	30	0	12	60	10	16
7	30	0	6	30	0	10	60	10	14

Interpretation of results:

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

Conclusions:

Under the conditions of this experiment the test material was found to cause a marked irritation when applied to the rabbit eye mucosa. Rinsing the eyes following instillation was of little but assessable effect

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Justification for classification or non-classification

Skin irritation - based on an erythema score of >2.3 and <4.0 for all animals, the classification is set as Cat 2. "Causes skin irritation"

Eye irritation - based on the scores for cornea of 4 and iris of 2 for all animals where the eye was not rinsed, classification should be Cat. 1 "Causes serious eye damage"