N'-(3-aminopropyl)-N,N-dimethylpropane-1,3-diamine

Endpoint summary

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

Study period:

from 1993-09-09 to 1994-01-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP, OCDE guideline 406 (1981 May the 12th)

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Centre d'élevage Lebeau, 78950 Gambais, France
- Age at study initiation: no data
- Weight at study initiation: 399+/-28g (Males), 391+/-39g (Females)
- Housing: individually
- Diet (e.g. ad libitum): ad libitum "Guinea pig sustenance reference 106 diet" (U.A.R., 91360 Villmoisson-sur-Orge, France)
- Water (e.g. ad libitum): drinking water filtered by a F.G. Milliporemembrane 0,22µ)
- Acclimation period: at least 5 days before the beginning of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3°C
- Humidity (%): 50+/-20%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To: 1993-10-08

Route:

intradermal and epicutaneous

Vehicle:

physiological saline

Concentration / amount:

intradermal induction phase: 1%
cutaneous induction phase: 25%
challenge phase: 10%

Route:

epicutaneous, occlusive

Vehicle:

physiological saline

Concentration / amount:

intradermal induction phase: 1%
cutaneous induction phase: 25%
challenge phase: 10%

No. of animals per dose:

control group: 10 animals (5 Males + 5 Females)
treated group: 20 animals (10 Males + 10 Females)

Details on study design:

RANGE FINDING TESTS:
Determination of the Minimum Irritant Concentration by intradermal route at increasing concentrations (1%, 10%, 25%). Result: MIC=1%
Determination of the Minimum Irritant Concentration (MIC) and the Maximal Non Irritant Concentration (MNIC) by cutaneous route at increasing concentrations (5%, 10%, 25%, 50%, 75%, 100%). Result: MIC= 25%, MNIC=10%.


MAIN STUDY
A. INDUCTION EXPOSURE

Intradermal induction D1
3injections on the scapular area:
. 0.1mL of Freund's complete adjuvant 50% in 0.9% NaCl
. 0.1mL of the test item 0.1% in water (treated group) or vehicle (control group)
. 0.1mL of a mixture 50/50 (V/V) of Freund complete adjuvant 50% in 0.9% NaCl and vehicle (for control group) or test item 1% in vehicle (for treated group)

Cutaneous induction D8
. On day 7, the irritation created with the application of sodium Laurylsulfate 10% in vaseline.
. On day 8, occlusive application on the scapular area of 0.5mL of the test item 25% (for treated group) or vehicle (for control group) for 48hours.


B. CHALLENGE EXPOSURE D22
On day 22, 24-hour occlusive application on the scapular area of 0.5mL of the test item 10% on the right flank and 0.5mL of the vehicle on the left flank.
Reactions are evaluated 24 and 48 hours after removal of the dressing.

Positive control substance(s):

yes

Remarks:

Dinitro 2,4 Chlorobenzene: Positive result in recent study (July 1993- CIT/Study No. 10829 TPG) on 5 females. Induction: test substance injected intradermally 0.05% (d1) and applied cutaneously 0.5% (d8) concentration. Challenge: 0,1% r flank 0.5% l flank

Positive control substance(s):

other: Dinitro 2,4 chlorobenzene

Statistics:

no

Positive control results:

Positive skin sensitization reactions in 5/5 female Guinea pigs (July 1993- CIT/Study No. 10829 TPG).

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No erythema/oedema

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: 10.0. Clinical observations: No erythema/oedema.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No erythema/oedema

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: 10.0. Clinical observations: No erythema/oedema.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10%

No. with + reactions:

6

Total no. in group:

19

Clinical observations:

well defined erythema/no oedema

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 6.0. Total no. in groups: 19.0. Clinical observations: well defined erythema/no oedema.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10%

No. with + reactions:

3

Total no. in group:

19

Clinical observations:

well defined erythema/no oedema

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 3.0. Total no. in groups: 19.0. Clinical observations: well defined erythema/no oedema.

Group	Sex	Animal	24h				48h
			Erythema		Oedema		Erythema		Oedema
			RF	LF	RF	LF	RF	LF	RF	LF
Control	M	21	0	0	0	0	0	0	0	0
		22	0	0	0	0	0	0	0	0
		23	0	0	0	0	0	0	0	0
		24	0	0	0	0	0	0	0	0
		25	0	0	0	0	0	0	0	0
Control	F	36	0	0	0	0	0	0	0	0
		37	0	0	0	0	0	0	0	0
		38	0	0	0	0	0	0	0	0
		39	0	0	0	0	0	0	0	0
		40	0	0	0	0	0	0	0	0
Treated	M	26	0	2	0	0	0	2/S	0	0
		27	0	1	0	0	0	0	0	0
		28	0	0	0	0	0	0	0	0
		29	0	2	0	0	0	2/S	0	0
		30	0	0	0	0	0	0	0	0
		31	0	2	0	0	0	1/S	0	0
		32	0	0	0	0	0	0	0	0
		33	0	0	0	0	0	0	0	0
		34	0	1	0	0	0	1/S	0	0
		35	0	1	0	0	0	1/S	0	0
Treated	F	41	0	1	0	0	0	1	0	0
		42	0	0	0	0	0	0	0	0
		43	0	0	0	0	0	0	0	0
		44	0	1	0	0	0	1	0	0
		45	0	0	0	0	0	0	0	0
		46	-	-	-	-	-	-	-	-
		47	0	1	0	0	0	1	0	0
		48	0	2	0	0	0	1/S	0	0
		49	0	2	0	0	0	1/S	0	0
		50	0	3	0	0	0	3/S	0	0

 S=Skin dryness

Interpretation of results:

other: Sensitiser cat. 1B

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

DIMETHYLDIPROPYLENETRIAMINE induced positive skin sensitization cutaneous reactions in 6/19 (32%) guinea pigs. The allergenicity level of the test substance was moderate (III) in guinea-pigs.

Executive summary:

The delayed contact hypersensivity of dimethyldipropylenetriamine (DMAPAPA) was evaluated in Guinea pigs according to OECD N°406 guideline (Magnusson and Kligman test). The induction phase has been realized both by intradermal route on day 1 (DMAPAPA 1% in vehicle) and by cutaneous route on day 8 (DMAPAPA 25%) in 2 groups of guinea pigs: 5 males and 5 females for control group and 10 males and 10 females for treated group. The challenge phase was realized on day 22 by cutaneous application of DMAPAPA 10%; the cutaneous reactions were scored 24 and 48 hours after the challenge phase. Only one female of the treated group died on day 9 but this death was not considered to be treatment-related. No cutaneous reaction was observed in the animals of the control group. In the treated group, inconclusive evidence of sensitisation skin reactions (very slight erythema: score of 1) were noted in 6/19 animals after 24 hours. Positive response characterised by a well defined and moderate erythema (scores of 2 and 3) were noted in 6/19 animals after 24 hours. In addition, a dryness of the skin was noted after 48 hours in 8/19 animals.

No oedema was noted. In conclusion, the allergenicity level of Dimethyldipropylenetriamine was moderate (III) in guinea pigs.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The delayed contact hypersensivity of N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine (DMAPAPA) was evaluated in Guinea pigs according to OECD N°406 guideline (Magnusson and Kligman test) (Clouzeau, 1994). The induction phase has been realized both by intradermal route on day 1 (DMAPAPA 1% in vehicle) and by cutaneous route on day 8 (DMAPAPA 25%) in 2 groups of guinea pigs: 5 males and 5 females for control group and 10 males and 10 females for treated group. The challenge phase was realized on day 22 by cutaneous application of DMAPAPA 10%; the cutaneous reactions were scored 24 and 48 hours after the challenge phase. Only one female of the treated group died on day 9 but this death was not considered to be treatment-related. No cutaneous reaction was observed in the animals of the control group. In the treated group, inconclusive evidence of sensitisation skin reactions (very slight erythema: score of 1) were noted in 6/19 animals after 24 hours. Positive response characterised by a well defined and moderate erythema (scores of 2 and 3) were noted in 6/19 animals after 24 hours. In addition, a dryness of the skin was noted after 48 hours in 8/19 animals. No oedema was noted. In conclusion, the allergenicity level of N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine was moderate (III) in guinea pigs.

Migrated from Short description of key information:
N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine induced skin sensitization cutaneous reactions in 6/19 (32%) guinea pigs. The allergenicity level of the test substance was moderate (III) in guinea-pigs.

Justification for selection of skin sensitisation endpoint:
Key study

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin sensitization:

In a test performed following theGPMT's method, 32% of the guinea pigs reacted to an induction concentration of 1% N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine. On the basis of this study and in accordance with Regulation (EC) No 1272/2008, N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine was classified as skin sensitizer category 1B (Hazard statement H317; May cause an allergic skin reaction) and in accordance with Annex VI of Commission Directive 2001/59/EC, N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine was classified as irritant with the symbol Xi and the phrase R43 ‘May cause sensitisation by skin contact’.