N,N-bis(3-aminopropyl)methylamine

Endpoint summary

Description of key information

The available skin and eye irritation/ corrosion studies showed that the test substance N, N-bis(3 -aminopropyl)methylamine can cause serious damage to skin and eye. Irreversible indications of skin and mucosa necrosis/ corrosion were observed after application of the undiluted test substance. Signs were milder when diluted solutions (< 15 % test substance solutions) were applied or when the exposure duration was shorter. 

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:

1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No GLP, no guideline was followed (published literature)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

, see below in "Principles of method"

Principles of method if other than guideline:

Male rabbits generally five per group were examined . Fur was carefully removed from the ventral skin, using an electric clipper . The rabbit was immobilized while 0.01 mL of sample was applied to the ventral skin. The dose site was not occluded during the contact period, which lasted 30 min or, if earlier, until the test material appeared to be completely absorbed or evaporated . At the end of the contact period, any remaining sample residue was removed with moist gauze and the rabbit was returned to its cage. After 18-24 h, the rabbits were again immobilized and the application site was swabbed with cottonwool moistened with lukewarm water (to enhance the visibility of any reaction), and the site was inspected for signs of local injury and inflammation . Additional sets of rabbits were tested using diluted sample, as required, to establish a dose response. The undiluted test material was also tested on occluded rabbit skin . For this procedure 0.5 mL (or 0 .5 g) of test material was applied to the shaven dorsal trunk skin and covered with a 1-in square gauze patch. Polyethylene sheeting was loosely wrapped around the animal's trunk and secured . During a 4-h contact period, the animal was restrained to avoid disturbing the dose site . Excess test material was carefully removed with cleansing tissue . Reactions were recorded at the end of the contact period and at 24 and 48 h following contact.

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Type of coverage:

other: In the first part of the experiment with the undiluted tets substance the dose site was not occluded. In the second part (new set of animals) using a diluted test substance the dose site was occluded.

Preparation of test site:

shaved

Vehicle:

other: In the first part of the experiment the undiluted test substance was applied. In the second part the test substance diluted in water was applied

Controls:

not required

Amount / concentration applied:

In the first part of the experiment 0.01 mL of the undiluted test substance was applied.
in the second part bof teh experiment 0.5 mL of the diluted (10 %) test substance was applied.

Duration of treatment / exposure:

In the first part (undiluted test substance) exposure duration of 30 minutes or until the test substance was absorbed,
In the second part (diluted test substance) 4 hours exposure duration.

Observation period:

In the first part (undiluted test substance) - 18 - 24 hours.
In the second part (diluted test substance) - 24 and 48 hours.

Number of animals:

5 animals

Details on study design:

TEST SITE
- Type of wrap if used: In the second part of the experiment polyethylene sheeting was loosely wrapped around the animal's trunk and secured.

REMOVAL OF TEST SUBSTANCE
- Washing: yes, at the end of the contact/ exposure period, any remaining sample residue was removed with moist gauze.

Irritation parameter:

other: necrosis

Basis:

mean

Time point:

other: 24 hours

Remarks on result:

other: Necrosis was observed in all animals applied with the undiluted tets substance

Irritation parameter:

other: irritaion, necrosis

Basis:

mean

Time point:

other: 24, 48 hours

Remarks on result:

other: No indications were observed when animals were treated with the diluted (10 %) test substance.

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin irritation/ corrosion

In the key study, (Myers, 1996), the test substance N,N-Bis(3-aminopropyl)methylamine was examined for its irritation/ corrosion potential in two following tests, in the first test the undiluted test substance was used and in the second part the diluted (10 %) test substance was applied. Each test was performed with different set of 5 male rabbits. Fur was carefully removed from the ventral skin, using an electric clipper. The rabbit was immobilized while 0.01 mL of sample was applied to the ventral skin. The dose site was not occluded during the contact period, which lasted 30 min. At the end of the contact period, any remaining sample residue was removed with moist gauze and the rabbit was returned to its cage. After 18-24 h, the rabbits were again immobilized and the application site was swabbed with cottonwool moistened with lukewarm water (to enhance the visibility of any reaction), and the site was inspected for signs of local injury and inflammation. Additional sets of rabbits were tested using diluted sample to establish a dose response. The undiluted test material was also tested on occluded rabbit skin. For this procedure 0.5 mL of test material was applied to the shaven dorsal trunk skin and covered with a 1-in square gauze patch. During a 4-h contact period, the animal was restrained to avoid disturbing the dose site . Excess test material was carefully removed with cleansing tissue . Reactions were recorded at the end of the contact period and at 24 and 48 h following contact.

In the first part of the test (undiluted test substance) necrosis was observed in all test animals. In the second part of the test (10 % test substance) no indications were observed.

In the supporting study (NTIS/OTS, 1992), the irritation/ corrosion effect of the test substance N,N-Bis(3-aminopropyl)methylamine was examined by application of the undiluted amine to the clipped belly skin of 2 rabbits. Severe necrosis was observed in 2/2 animals examined. In a following study a 10% solution of the test substance in acetone produced capillary injection of erythema grade 6 (out of 10) (moderate irrittaion) in all 5 rabbits examined. The results of the study suggest that the (undiluted) test substance is a necrotic agent (corrosive).

Eye irritation/ corrosion

In the key study (Myers, 1996) the test substance N, N-bis(3-aminopropyl)methylamine was examined for its eye irritation/ corrosion effect in male rabbits (5 rabbits per dose). 0.005 mL of the undiluted test substance was instilled with a pipette direct on the cornea. 0.5 mL of 5 % and 15 % solutions of the test substance in water were instilled by syringe into the inferior conjunctival sac. The eyes were washed 24 hours after application and examined with fluorescein. Treatment with 0.005 mL of the undiluted test substance and 0.5 mL of the 15 % solution of the test substance caused severe corneal opacity and iritis. Minor cornea opacity and iritis were observed following a treatment with 5 % of the test substance solution.

In the supporting study (NTIS/OTS, 1992), the test substance Bis-(3-aminopropyl-)methylamine was tested for its eye irritation/ corrosion effect in a set of few experiments in rabbits. In these tests 0.005 mL of the undiluted test substance, and 0.5 mL of the test substance in concentrtaions/ dilutions of 15 % (in water and in propylene glycol) and 5 % (in ethylene glycol) were applied to the conjunctival sac of 5 rabbits per dose. After 24 hours the eyes were examined with fluorescein. Severe eye injury with iritis and corneal necrosis resulted from instillation of the undiluted or diluted (15 % in distilled water/ ethylene glycol) were observed. An excess of 5 % solution (in ethylene glycol) caused damage, graded 8 out of 10.

In the supporting study (BASF, 1978), the test substance Bis-(3-aminopropyl-)methylamine was examined for its eye irritation/ corrosion potential in rabbits. The test substance caused an irriversible damage within 8 days of observation. 1 hour after application the following signs were observed: nictitating membrane red, very stong opacity, weak oedema, bloody secretion. 24 hours after application a stronger opacity and oedema were observed together with necrotic signs of the lid. 8 days after application the eyes showed additionally signs of corrosion and ulceration.

Justification for classification or non-classification

Based on the results obtained Bis-(3-aminopropyl-)methylamine is classified as Skin Corr. 1B (H314) - causes severe skin burns and eye damage according to Regulation (EC) No 1272/2008 (CLP).