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

Endpoint summary

Description of key information

N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine is corrosive to the skin and the eyes.

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:

from 1991-02-01 to 1991-06-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP, OECD guideline n°404 (1981 May 12th)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage cunicole du val de Selle, 80160 Prouzel, France
- Age at study initiation: no data
- Weight at study initiation: 2500+/-100 g
- Housing: individually
- Diet (e.g. ad libitum): ad libitum pellet diet "Rabbits sustenanceref.112C (U.A.R., 91360 Villemoisson-sur-Orge, France)"
- Water (e.g. ad libitum): ad libitum tap water filtered by a 0.22µ filter membrane (Cociété Millipore, 78140 Vélizy, France)
- Acclimation period: at least 5 days before treatment
- Other: Male rabbits were used


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/-3°C
- Humidity (%): 50+/-20%
- Air changes (per hr): non recycled and filtered with absolute filters
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL undiluted

Duration of treatment / exposure:

4 hours (n=3) and 3 minutes (n=1)

Observation period:

1, 24, 48, 72hours then daily until day 15

Number of animals:

4 in total

Details on study design:

TEST SITE
- Area of exposure: 6cm² dry gauze patch (Semes France, 54183 Heillecourt, France)
- Type of wrap if used: adhesive hypoallergenic aerated semi-occlusive dressing (Laboratoires de Pansements et d'hygiène, 21300 Chenôve, France) attached to a gauze bandage (Promotion médicale, 27000 Evreux, France)

SCORING SYSTEM: according to the OECD guideline n° 404 (1981 May 12th)

Irritation parameter:

erythema score

Remarks:

4-hour exposure

Basis:

animal: #1, 2 and 3

Time point:

other: 24, 48 hours

Reversibility:

not reversible

Remarks:

, sacrificed on D2 for humanitarian reasons

Remarks on result:

other: Necrosis

Irritation parameter:

edema score

Remarks:

4-hour exposure

Basis:

animal #1

Time point:

other: 24, 48 hours

Score:

2

Max. score:

4

Irritation parameter:

edema score

Remarks:

4-hour exposure

Basis:

animal: #2 and 3

Time point:

other: 24, 48 hours

Score:

4

Max. score:

4

Irritation parameter:

erythema score

Remarks:

3-min exposure

Basis:

animal #4

Time point:

other: D1 to D15

Reversibility:

not reversible

Remarks on result:

other: Necrosis

Irritation parameter:

edema score

Remarks:

3-min exposure

Basis:

animal #4

Time point:

other: 24, 48 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

The application of the test substance during 4 hours (animals O1 to O3) has induced a tissular destruction on the whole depth of the skin the 3 animals which were sacrificed for humanitarian reasons.
After the application of the test substance during 3 minutes (animal O4), severe erythema to slight eschar formation (superficial necrosis) was observed after one hour and then was irreversible during 14 days. A slight oedema (score 2) was noted during 24 hours.

Individual scoring

TD=Tissue Destruction N=Necrosis

	D1	D2	D3	D4	D5	D6	D7	D8	D9	D10	D11	D12	D13	D14	D15
Erythema
O1	TD	TD	-	-	-	-	-	-	-	-	-	-	-	-	-
O2	TD	TD	-	-	-	-	-	-	-	-	-	-	-	-	-
O3	TD	TD	-	-	-	-	-	-	-	-	-	-	-	-	-
O4	N	N	N	N	N	N	N	N	N	N	N	N	N	N	N
Oedema
O1	2	2	-	-	-	-	-	-	-	-	-	-	-	-	-
O2	4	4	-	-	-	-	-	-	-	-	-	-	-	-	-
O3	4	4	-	-	-	-	-	-	-	-	-	-	-	-	-
O4	2	2	0	0	0	0	0	0	0	0	0	0	0	0	0

Interpretation of results:

Category 1A (corrosive)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

DIMETHYLDIPROPYLENETRIAMINE has to be labelled as corrosive in rabbits.

Executive summary:

The acute dermal irritation of Dimethyldipropylenetriamine (DMAPAPA) was evaluated in male New Zealand White rabbits according to OECD N° 404 Guideline. 0,5mL of DMAPAPA was applied during 4 hours in 3 rabbits and during 3 minutes in 1 rabbit on clipped area. The cutaneous reaction was observed 1, 24, 48, 72 hours after removal of the dressing and then daily to day 15 (for 1 animal).

After application of the substance during 4 hours, tissular destruction on the whole depth of the skin was observed in the three animals, which were sacrificed for ethical reasons. The application of DMAPAPA during 3 minutes induced a severe erythema and a slight eschar formation in 1 hour that were irreversible during 14 days. A slight oedema was noted during 24 hours.

Under these experimental conditions, DMAPAPA has to be classified as corrosive in rabbits.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Species:

rabbit

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation-Corrosion

In vitro study

To evaluate the potential skin corrosivity of N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine, the pH and acidic/alkaline reserve was measured according to the method described by Froment (1993) (Régnier and Imbert, 1992). 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
N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine	12.0	1.76	13.7

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/or I≥ 10.

N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine is considered as potentially corrosive to the skin.

In vivo studies

The dermal irritation of N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine (DMAPAPA) was evaluated in male New Zealand White rabbits according to OECD N° 404 Guideline (Clouzeau 1991). After application of the substance during 4 hours, tissular destruction on the whole depth of the skin was observed in the three animals. The application of DMAPAPA during 3 minutes induced a severe erythema and a slight eschar formation in 1 hour that were irreversible during 14 days. A slight oedema was noted during 24 hours. DMAPAPA was therefore considered as corrosive.

In a BASF study, DMAPAPA was shown to be corrosive after occlusive application for 3 and 60 min in two rabbits. After 24 h haemorrhages occurred in the 3 min exposure group and after a 1 h exposure necrosis was found. At the end of the observation period after 8 days full thickness necrosis were found (BASF 1961).

Eye irritation-Corrosion

In vitro study

To evaluate the potential corrosivity for the eye of N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine, the pH and acidic/alkaline reserve was measured according to the method described by Froment (1993) (Régnier and Imbert, 1992). 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
N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine	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.

N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine is considered as potentially severely irritating to the eye.

In vivo studies

No data available.

Respiratory tract irritation

This information is not available.

Justification for selection of skin irritation / corrosion endpoint:
Key study

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Skin irritation:

N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine induced skin corrosion after a 3 -min exposure. On this basis and in accordance with Regulation (EC) No 1272/2008, N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine was classified as corrosive category 1A (Hazard statment H314: Causes severe skin burnsand eye damage) and in accordance with Annex VI of Commission Directive 2001/59/EC, N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine was classified as corrosive with the symbol C and the phrase R35 "Causes severe burns".

Eye irritation:

N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine is classified as corrosive to the skin. On this basis and in accordance with Regulation (EC) No 1272/2008 N'-(3-aminopropyl) -N, N-dimethylpropane-1,3-diamine was classified as irritating to eyes caregory 1 (H318: Causes serious eye damage).

Respiratory tract irritation: