3-aminopropyldiethylamine

Endpoint summary

Description of key information

3-aminopropyldiethylamine was shown to be corrosive to the skin and eye and irritating to the respiratory tract.

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:

02. May 1961 - 19. May 1961

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented report which meets basic scientific principles.

Principles of method if other than guideline:

Two animals were treated for 1, 5, 15 min using occlusive conditions. An application site of 2.5x2.5 cm was covered with the liquid test substance. After the application time (1, 5, 15 min) the skin was washed with Lutrol (conc.) and Lutrol/water (1:1). The animals were observed for 8 days and skin changes were recorded daily. The report describes findings after 24 hours and at the end of the observation period (8 days). For a final evaluation, the findings after 48 and 72 hours from the raw data were taken into account.

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.02 and 2.31 kg

Type of coverage:

occlusive

Preparation of test site:

other: intact skin

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Duration of treatment / exposure:

1 min, 5 min and 15 min

Observation period:

14 days

Number of animals:

2

Details on study design:

TEST SITE
- Area of exposure: 2.5x2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The skin was washed with Lutrol (conc.) and Lutrol/water (1:1)
- Time after start of exposure: 1, 5 or 15 min

Irritation parameter:

other: Necrosis

Time point:

other: 24 h to 8 day

Reversibility:

not reversible

Remarks on result:

other: Exposure time: 1, 5 or 15 min

The application of the test substance caused necrosis to the exposes tissues and therefore a precise evaluation of erythema and edema scores was not possible.

Major findings after 1, 5 or 15 min exposure: After 24 h leather-like brown-reddish necrosis with partly reddish partly anaemic surroundings was observed. 8 days post application hard, almost black necrosis was observed.

Interpretation of results:

Category 1A (corrosive)

Executive summary:

Two animals were treated for 1, 5, 15 min using occlusive conditions with 3-aminopropyldiethylamine. An application site of 2.5x2.5 cm was covered with the liquid test substance. After the application time (1, 5, 15 min) the skin was washed with Lutrol (conc.) and Lutrol/water (1:1). The animals were observed for 8 days and skin changes were recorded daily. The report describes findings after 24 hours and at the end of the observation period (8 days). For a final evaluation, the findings after 48 and 72 hours from the raw data were taken into account. Twenty-four hours after the 1, 5 or 15-min exposure, leather-like brown-reddish necrosis with partly reddish partly anaemic surroundings was observed. Eight days post application hard, almost black necrosis was observed.

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:

03. May 1961 - 12. May 1961

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented report which meets basic scientific principles.

Principles of method if other than guideline:

50 µL of the test substance were applied to the conjunctival sac of one eye in 2 animals. The animals were observed after 10 min, 1 and 3h on the day of treatment and up to 8 days afterwards. Findings were recorded daily. The eyes were not washed out after 24 hours as specified in OECD Guideline 405. The report describes findings after 1 and 24 hours and at the end of the observation period. For final evaluation, the findings after 48 and 72 hours from the raw data were taken into account.

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.01 and 3.23 kg

Vehicle:

unchanged (no vehicle)

Controls:

other: The adjacent eye served as control treated with 0.9 % NaCl (saline).

Duration of treatment / exposure:

single application

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

2

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 h - 48 h - 72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks:

corrosion/eye leakage

Remarks on result:

other: necrosis

Other effects:

Gross pathology: 1 animal with invagination of the eye and 1 animal with phanophtalmia.

The application of the test substance caused necrosis and suppuration to the eyes and therefor a precise evaluation of edema and iritis scores was not possible.

Shortly after exposure (10 min) animals showed bloody eye discharge and corrosion was noted. After 2 days, swelling of the eyelids was observed. 5 days post application vessel ingrow (animal1) and suppuration (animal2) was noted. Animal 1 was sacrificed ahead of schedule on day 5 (complete leakage of eye).

Interpretation of results:

Category 1 (irreversible effects on the eye)

Executive summary:

Fifty µL of 3-aminopropyldiethylamine were applied to the conjunctival sac of one eye in 2 animals. The animals were observed after 10 min, 1 and 3h on the day of treatment and up to 8 days afterwards. Findings were recorded daily. The eyes were not washed out after 24 hours.The application of the test substance caused necrosis and suppuration to the eyes and therefore a precise evaluation of edema and iritis scores was not possible. Shortly after exposure (10 min) animals showed bloody eye discharge and corrosion was noted. After 2 days, swelling of the eyelids was observed. Five days post application vessel ingrow (animal 1) and suppuration (animal 2) was noted. Animal 1 was sacrificed ahead of schedule on day 5 (complete leakage of eye).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin Irritation-Corrosion

In vitro studies

To evaluate the potential skin corrosivity of 3-aminopropyldiethylamine, the pH and acidic/alkaline reserve was measured according to the method described by Regnier and Imbert (ATLA, 1992, 20, 457-465) and Froment (Arkema unpublished data, 1993). Under the test conditions, the results are as follow:

 

Test item	pH	log R (acidic/alkaline reserve	Physical-chemical index (I) I = pH + log R, for pH =7 I = (14 -pH) + log R, for pH < 7
3-aminopropyldiethylamine	11.9	1.6	13.5

 

According to the method, a substance is considered as potentially corrosive to the skin if at least 2 of the 3 following criteria are fulfilled:

pH= 2.5 or pH =9.5; log R = 0 and/ot I= 10.

3-aminopropyldiethylamine is considered as potentially corrosive to the skin.

In vivo studies

In a key study (BASF, 1961), two animals were treated for 1, 5, 15 min using occlusive conditions with 3-aminopropyldiethylamine. An application site of 2.5x2.5 cm was covered with the liquid test substance. After the application time (1, 5, 15 min) the skin was washed with Lutrol (conc.) and Lutrol/water (1:1). The animals were observed for 8 days and skin changes were recorded daily. The report describes findings after 24 hours and at the end of the observation period (8 days). For a final evaluation, the findings after 48 and 72 hours from the raw data were taken into account. Twenty-four hours after the 1, 5 or 15-min exposure, leather-like brown-reddish necrosis with partly reddish partly anaemic surroundings was observed. Eight days post application hard, almost black necrosis was observed.

In a suporting study (Clouzeau, 1988), the acute dermal irritation of 3-aminopropyldiethylamine was evaluated inalbino rabbits. 0.5 mL of the test substance was applied during 4 hours in 1 rabbit on the right clipped flank. The left untreated flank was used as negative control. The cutaneous reaction was observed one hour, 24, 48, 72 hours after removal of the dressing. After 1 hour, 24, 48 and 72 hours, a tissular necrosis was noted on the site of the cutaneous application. The rabbit has been sacrificed for ethical reasons 72 hours after the end of exposition.

Eye irritation-Corrosion

In vitro studies

To evaluate the potential skin corrosivity of 3-aminopropyldiethylamine, the pH and acidic/alkaline reserve was measured according to the method described by Regnier and Imbert (ATLA, 1992, 20, 457-465) and Froment (Arkema unpublished data, 1993). Under the test conditions, the results are as follow:

 

Test item	pH	log R (acidic/alkaline reserve	Physical-chemical index (I) I = pH + log R, for pH =7 I = (14 -pH) + log R, for pH < 7
3-aminopropyldiethylamine	11.9	1.6	13.5

 

According to the method, a substance is considered as potentially corrosive to the eye if at least 2 of the 3 following criteria are fulfilled:

pH= 2.5 or pH =9.5; log R = 0 and /or I= 9.

3-aminopropyldiethylamine is considered as potentially severely irritating to the eye.

In vivo studies

In a key study (BASF, 1961), fifty µL of 3-aminopropyldiethylamine were applied to the conjunctival sac of one eye in 2 animals. The animals were observed after 10 min, 1 and 3 h on the day of treatment and up to 8 days afterwards. Findings were recorded daily. The eyes were not washed out after 24 hours. The application of the test substance caused necrosis and suppuration to the eyes and therefore a precise evaluation of edema and iritis scores was not possible. Shortly after exposure (10 min) animals showed bloody eye discharge and corrosion was noted. After 2 days, swelling of the eyelids was observed. Five days post application vessel ingrow (animal 1) and suppuration (animal 2) was noted. Animal 1 was sacrificed ahead of schedule on day 5 (complete leakage of eye)

Justification for classification or non-classification

According to the harmonised classification and labelling (CLP) approved by the European Union:

- Skin Corr. 1B, H314

- Eye Irrit. 1, H318

Self classification according to CLP criteria:

- Skin Corr. 1A, H314

- Eye Irrit. 1, H318

- STOT-SE 3, H335