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Skin sensitisation

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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
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

Constituent 1
Chemical structure
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-isopropoxypropylamine
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)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Concentration / amount:
intradermal induction: 0.1%
cutaneous induction: 25%
cutaneous challenge:10%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
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)

Resultsopen allclose all
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.
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.
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.
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.