3-isopropoxypropylamine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

end 1998-05-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP, OECD 406 (July 17th 1992)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

study performed before the implementation of reach regulation.

Test material

Test material information

Constituent 1

Reference substance name:

3-isopropoxypropylamine

EC Number:

220-816-2

EC Name:

3-isopropoxypropylamine

Cas Number:

2906-12-9

Molecular formula:

C6H15NO

IUPAC Name:

3-(propan-2-yloxy)propan-1-amine

Details on test material:

- Name of test material (as cited in study report): 3-isopropoxypropylamine
- Physical state: liquid
- Analytical purity: 99.78%
- Purity test date: 1997-08-07
- Lot/batch No.: 9708P0073
- Expiration date of the lot/batch: December 1998
- Stability under test conditions: no data
- Storage condition of test material: at room temperature and protected from light
- Other: origin: Usine de Maurienne, La Chambre

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River France, 76410 Saint Aubin lès Elbeuf, France
- Age at study initiation: approx. 3months old
- Weight at study initiation: 353+/-10g (males) and 355+/-21g (females)
- Housing: individually in polycarbonates cages (48x27x20cm)
- Diet (e.g. ad libitum): ad libitum 106pelleted diet (U.A.R. 91360 Villemoisson sur Orge, France)
- Water (e.g. ad libitum): ad libitum drinking water filtered with a F.G. Millipore (0.22µ)
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/-2°C
- Humidity (%): 30-70%
- Air changes (per hr): approx. 12 cycles
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 1997-10-09 To: 1997-11-10

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

physiological saline

Induction 2

Concentration / amount:

intradermal induction: 0.1%
cutaneous induction: 25%
cutaneous challenge:10%

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

physiological saline

Challenge 2

Concentration / amount:

intradermal induction: 0.1%
cutaneous induction: 25%
cutaneous challenge:10%

No. of animals per dose:

control group: 5males and 5females
treated group: 10males and 10females

Details on study design:

RANGE FINDING TESTS: determination of the maximum non irritant concentrations
Intradermal: injection of 0.1mL of formulations at 0.1, 1, 5 and 10mg/kg +/-FCA on clipped area. Evaluation of cutaneous reactions at 24 and 48hours after removal of the dressing.
Cutaneous: occlusive application for 24h of 0.5mL of formulations at 5, 10, 25 and 50mg/kg on clipped area. Evaluation of cutaneous reactions at 24 and 48hours after removal of the dressing.


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 IPOPA 0.1% in 0.9% NaCl (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 IPOPA 0.1% in 0.9% NaCl (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 IPOPA 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 IPOPA 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:

Dinitrochlorobenzene and Mercaptobenzothiazole

Results and discussion

Positive control results:

CIT Study N°16065 TSG: Spetember 1997. Under these experimental conditions, Dinitrochlorobenzene at the concentration of 1% induced positive skin sensitization reactions in 90% of the guinea pigs. Mercaptobenzothiazole at the concentration of 20% induced positive skin reaction in 30% of the guinea pigs.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

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.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

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.

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10%

No. with + reactions:

13

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 13.0. Total no. in groups: 20.0.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10%

No. with + reactions:

1

Total no. in group:

20

Clinical observations:

dryness of the skin (14/20), crusts (1/20)

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: dryness of the skin (14/20), crusts (1/20).

Any other information on results incl. tables

Scoring of skin reactions

LF=left flank

RF=right flank

S=dryness of the skin

A=crusts

Group	Sex	Animal	24h				48h
			Erythema		Oedema		Erythema		Oedema
			LF	RF	LF	RF	LF	RF	LF	RF
Control	M	136	0	0	0	0	0	0	0	0
		137	0	0	0	0	0	0	0	0
		138	0	0	0	0	0	0	0	0
		139	0	0	0	0	0	0	0	0
		140	0	0	0	0	0	0	0	0
Control	F	141	0	0	0	0	0	0	0	0
		142	0	0	0	0	0	0	0	0
		143	0	0	0	0	0	0	0	0
		144	0	0	0	0	0	0	0	0
		145	0	0	0	0	0	0	0	0
Treated	M	146	0	0	0	0	0	0	0	0
		147	0	2	0	2	0	2/S	0	0
		148	0	1	0	0	0	1/S	0	0
		149	0	2	0	0	0	0/S	0	0
		150	0	2	0	2	0	1/S/A	0	0
		151	0	1	0	0	0	0	0	0
		152	0	2	0	0	0	0/S	0	0
		153	0	2	0	2	0	1/S	0	0
		154	0	2	0	0	0	0/S	0	0
		155	0	1	0	0	0	0/S	0	0
Treated	F	156	0	2	0	0	0	1/S	0	0
		157	0	2	0	0	0	0/S	0	0
		158	0	1	0	0	0	0	0	0
		159	0	2	0	0	0	0/S	0	0
		160	0	2	0	0	0	0/S	0	0
		161	0	1	0	0	0	1/S	0	0
		162	0	2	0	0	0	0	0	0
		163	0	1	0	0	0	0	0	0
		164	0	2	0	0	0	0/S	0	0
		165	0	2	0	0	0	0	0	0

 

Applicant's summary and conclusion

Interpretation of results:

other: sensitising Cat. 1A

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

3-Isopropoxyproylamine induces delayed contact hypersensitivity in 65% and should be considered as a strong sensitiser.

Executive summary:

The delayed contact hypersensivity of 3-isopropoxypropylamine (IPOPA) was evaluated in Guinea pigs according a protocol similar to OECD N°406 guideline (Magnusson and Kligman test) (Manciaux, 1998b). The induction phase has been realized both by intradermal route on day 1 (IPOPA 0.1% in vehicle) and by cutaneous route on day 8 (IPOPA 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 IPOPA 10%; the cutaneous reactions were scored 24 and 48 hours after the challenge phase. No cutaneous reaction was observed in the animals of the control group. In the treated group, a very slight or well-defined erythema (grade 1 or 2) was noted at the 24hour reading in 6/20 and 13/20 guinea pigs respectively. A slight oedema (grade 2) was recorded in 3/20 animals. At the 48hour reading, a very slight or well-defined erythema (grade 1 or 2) persisted in 5/20 and 1/20 animals respectively. Dryness of the skin was observed in 14/20 animals and crusts were noted in one animal. 3-isoproxypropylamine induces delayed contact hypersensitivity in 65% and should be considered as a strong sensitiser.