N'-[3-(dimethylamino)propyl]-N,N-dimethylpropane-1,3-diamine

Endpoint summary

Description of key information

N'-[3-(dimethylamino)propyl]-N,N-dimethylpropane-1,3-diamine was not skin sensitizing in a GPMT.

 

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study with GLP

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

Cited as Directive 84/449/EEC, B.6

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

LLNA method was not available by the time the study was conducted

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Lippische Versuchstierzucht, Hagemann GmbH & Co. KG, Extertal, Germany
- Age at study initiation: young adult animals
- Weight at study initiation: 292 - 341 g
- Housing: 5 animals per cage
- Diet: Kliba Labordiaet 341 (Kaninchen-Meerschweinchen-Haltungsdiaet), ad libitum
- Water: tap water ad libitum (about 2 g of ascorbic acid per 10 L water was added to the drinking water twice a week).
- Acclimation period: 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

The feed used in the study was assayed for chemical and microbiological contaminants. The dinking water is regularly assayed for chemical contaminants by the municipal authorities of Frankenthal and the Technical Services of BASF AG as well as for the presence of germs by a contract laboratory.

Route:

intradermal and epicutaneous

Vehicle:

water

Concentration / amount:

Intradermal induction: test substance 0.1 % in 0.9% aqueous NaCl-solution or in Freund's adjuvant/0.9% aqueous NaCl-solution (1:1) or 0.9% aqueous NaCl-solution.
Percutaneous induction: test substance 1 % in aqua bidest.
Challenge: test substance 0.5 % in aqua bidest.
(concentrations were selected on the basis of a pretest)

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

Intradermal induction: test substance 0.1 % in 0.9% aqueous NaCl-solution or in Freund's adjuvant/0.9% aqueous NaCl-solution (1:1) or 0.9% aqueous NaCl-solution.
Percutaneous induction: test substance 1 % in aqua bidest.
Challenge: test substance 0.5 % in aqua bidest.
(concentrations were selected on the basis of a pretest)

No. of animals per dose:

Test group: 10
Control groups: 5/group (2 control group)

Details on study design:

RANGE FINDING TESTS:
2 x 2 cm filter paper strips soaked in the test substance formulation (about 0.15 g) were applied to the skin of the flanks under an occlusive dressing. The test substance was applied 2 times for 24 h within a period of 96 hours in order to detect non-specific phenomena that are not caused by a sensitisation reaction but could possibly be attributed to a shift in the irritation threshold.
- Site of application: flank
- No. of animals: 4 per test concentration
- Readings: about 24 and 48 h after the beginning of application
- Evaluation: according to the Draize Scoring System

MAIN STUDY

A. 1) INDUCTION EXPOSURE (intradermal)
- No. of exposures: 6 intradermal injections in groups of two per animal
- Test group (10 animals): front row: 2 injections each of 0.1 mL Freund's adjuvant without test substance emulsified with 0.9% aqueous NaCl-solution in a ratio of 1:1; middle row: 2 injections each of 0.1 mL of the test substance formulation; back row: 2 injections each of 0.1 mL Freund's adjuvant/0.9% aqueous NaCl-solution (1:1) with test substance
- Control groups (5 animals per group): The animals were given the same injections but without test subtsance, only with the formulating agent
- Site: shoulder
- Readings: 24 h after the beginning of application
- Evaluation: according to the Draize Scoring System

2) INDUCTION EXPOSURE (percutaneous)
- No. of exposures: 1 percutaneous exposure 1 week after intradermal induction
- Amount applied: 2 x 4 cm filter paper strips soaked in the test substance formulation (about 0.3 g) were applied to the skin of the shoulder under an occlusive dressing
- Exposure period: percutaneous exposure: 48 h
- Control groups: no treatment
- Site of application: shoulder, same area as intradermal application
- Readings: 24 h after the beginning of application
- Evaluation: according to the Draize Scoring System

B. CHALLENGE EXPOSURE
- No. of exposures: single percutaneous exposure
- Duration of exposure: 24 h
- Day of challenge: 21 days after intradermal induction
- Site: intact flank
- Concentrations: non-irritant concentration (2 x 2 cm filter paper strips soaked with about 0.15 g of the test substance formulation)
- Control groups: control group 1 treated like test group; control group 2 remained untreated
- Evaluation (hr after challenge): 24 and 48 h after removal of the patch
- Site of application: intact flank

Positive control substance(s):

yes

Remarks:

Performed in a separate study twice a year in the laboratory with alpha-hexylcinnamaldehyde.

Group:

positive control

Remarks on result:

other: Performed in a separate study twice a year in the laboratory with alpha-hexylcinnamaldehyde.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0.5%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.5%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0.5%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.5%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5%. No with. + reactions: 0.0. Total no. in groups: 10.0.

The intradermal induction with 0.1% test substance preparations caused well-defined erythema and slight edema were observed at the injection sites of the control group animals and test group animals. The control group animals which were treated with 0.9% aqueous NaCl-solution did not show any skin reactions.

After the percutaneous induction with a 1% test substance preparation incrustation, partially open (caused by the intradermal induction) could be observed in addition to well-defined erythema and slight edema in all test group animals.

After the challenge with a 0.5 % test substance preparation the animals of control group and the test group, animals did not show any skin reactions 24 and 48 hours after removal of the patches.

Interpretation of results:

not sensitising

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Additional information:

In a guinea pig maximization test according to EU method B.6, BIS-DMAPA was investigated with male and female Dunkin-Hartley guinea pigs (BASF AG, 1993). The study examined the skin sensitising effect on guinea pigs, using 20 animals in total. Positive and negative controls were included in the study. Animals were induced with 0.1% (intradermal induction) and 1% (percutaneous induction) and challenged with 0.5% Bis-DMAPA. Based upon the observations made in the assay, the substance didn’t cause skin sensitisation in guinea pigs.

 

 

 

Justification for classification or non-classification

Classification,Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008, as amended for the third time in Directive (EC 618/2012).

There is no information available, that N'-[3-(dimethylamino)propyl]-N,N-dimethylpropane-1,3-diamine is a sensitizer of the respiratory tract.