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Description of key information

Skin sensitisation

The delayed contact hypersensivity of was evaluated in Guinea pigs according to OECD N°406 guideline (Magnusson and Kligman test) (Guillot, 1990a).

The induction phase has been realized both by intradermal route on day 1 (0.5% in vehicle) and by cutaneous route on day 9 (2.5%) in 2 groups of guinea pigs: 10 males and 10 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 0.25 and 0.5 % on the left flank (vehicle on the right flank); the cutaneous reactions were scored 5, 24 and 48 hours after the challenge phase.

From the macroscopic and histological results obtained under the experimental conditions it may be concluded that the test article provoked:

- In the 10 guinea-pigs of the group treated with the test article in a 0.25% solution, reactions of sensitization in 3 animals, reactions of mixed type (allergy and orthoergy) in 4 guinea-pigs and lesions of orthoergic intolerance in the 3 other animals, this last phenomenon can hide possible reactions of allergic type.

- In the 10 guinea-pigs of the group treated with the test article in a 0.5% solution, reactions of sensitization in 4 animals, and lesions of orthoergic intolerance in 5 other guinea-pigs, this last phenomenon can hide possible reactions of allergic type.

No significant abnormality was noted in the 10 animals of each one of both control groups treated at the same concentrations.

ln both cases and like during the previous study (Guillot, 1990b) carried out with the test article in a 1% solution, the sample studied can be considered as a caustic allergen.

Under these experimental conditions and according to the Magnusson and Kligman method, the test item MONO-n-HEPTYLAMINE at the concentration of 0.25 % induced positive skin sensitization reactions in 7/10 guinea pigs, and at the concentration of 0.5% induced positive skin sensitization reactions in 4/10 guinea pigs. The test item is considered as sensitizing to the guinea pig.

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:
1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
This study was performed before the implementation of the REACH regulation.
Test material information:
Composition 1
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Shamrock Bioservices - 12, route de Saint Côme - 78950 Gambais - France.
- Age at study initiation: no data
- Weight at study initiation: 329 to 400g
- Housing: housing by groups of 5 (or of 2 for the preliminary studies), in polystyrene cages
- Diet: Guinea-pig complete pelleted maintenance food, ad libitum
- Water: Softened and filtered drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3° C.
- Humidity (%): 30 to 70% R.H.
- Photoperiod (hrs dark / hrs light): 12h/12h

Route:
intradermal
Vehicle:
water
Concentration / amount:
Intrademal injection: 0.5% (V/V)
Day(s)/duration:
Single
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Topical application: 2.5% (V/V)
Day(s)/duration:
Single
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Challenge application: 0.25 and 0.5% (V/V)
No. of animals per dose:
Control: 10 males and 10 females
Treated: 10 males and 10 females
Details on study design:
RANGE FINDING TESTS: concentrations: 0.25, 0.5, 1, 2.5, and 5% (V/V) (cf rapport H-IFT n°607331)

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2: 3 series of 2 intradermal injections + 1 occlusive topical application
- Exposure period: D1: intrademal injections, D9: occlusive topical application for 48 hours
- Test groups:
Intradermal: adjuvant +/- test article in the vehicle
Topical: test article in the vehicle
- Control group:
Intradermal: adjuvant +/- vehicle alone
Topical: vehicle alone
- Site: interscapular region
- Duration: 10 days
- Concentrations: intrademal injection: 0.5% (V/V) and topical application: 2.5% (V/V)

B. CHALLENGE EXPOSURE
- No. of exposures: 1 occlusive topical application of the test article and of the vehicle alone
- Day(s) of challenge: Day 22
- Exposure period: 24 hours
- Test groups: vehicle alone + test article in the vehicle
- Control group: vehicle alone + test article in the vehicle
- Site: test article on the left flank
- Concentrations: 0.25 and 0.5%
- Evaluation (hr after challenge): 5, 24 and 48 hours after removal of the occlusive patch
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.25%
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.25%. No with. + reactions: 2.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.25%
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: 0.25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.25%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
10/10 animals with reactions at challenge site, including 7/10 animals sensitized
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.25%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: 10/10 animals with reactions at challenge site, including 7/10 animals sensitized.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
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: negative control. Dose level: 0.5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
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: negative control. Dose level: 0.5%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.5%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
10/10 animals with reactions at challenge site, including 4/10 animals sensitized
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: 10/10 animals with reactions at challenge site, including 4/10 animals sensitized.
Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
Under these experimental conditions and according to the Magnusson and Kligman method, the test item MONO-n-HEPTYLAMINE
at the concentration of 0.25 % induced positive skin sensitization reactions in 7/10 guinea pigs, and at the concentration of 0.5% induced positive skin sensitization reactions in 4/10 guinea pigs. The test item is considered as sensitizing to the guinea pig.
Executive summary:

The delayed contact hypersensivity of 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 (0.5% in vehicle) and by cutaneous route on day 9 (2.5%) in 2 groups of guinea pigs: 10 males and 10 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 0.25 and 0.5 % on the left flank (vehicle on the right flank); the cutaneous reactions were scored 5, 24 and 48 hours after the challenge phase.

From the macroscopic and histological results obtained under the experimental conditions it may be concluded that the test article provoked:

- In the 10 guinea-pigs of the group treated with the test article in a 0.25% solution, reactions of sensitization in 3 animals, reactions of mixed type (allergy and orthoergy) in 4 guinea-pigs and lesions of orthoergic intolerance in the 3 other animals, this last phenomenon can hide possible reactions of allergic type.

- In the 10 guinea-pigs of the group treated with the test article in a 0.5% solution, reactions of sensitization in 4 animals, and lesions of orthoergic intolerance in 5 other guinea-pigs, this last phenomenon can hide possible reactions of allergic type.

No significant abnormality was noted in the 10 animals of each one of both control groups treated at the same concentrations.

ln both cases and like during the previous study carried out with the test article in a 1% solution, the sample studied can be considered as a caustic allergen.

Under these experimental conditions and according to the Magnusson and Kligman method, the test item MONO-n-HEPTYLAMINE

at the concentration of 0.25 % induced positive skin sensitization reactions in 7/10 guinea pigs, and at the concentration of 0.5% induced positive skin sensitization reactions in 4/10 guinea pigs. The test item is considered as sensitizing to the guinea pig.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Justification for classification or non-classification

According to CLP regulation, Heptylamine should be considered classified as skin sensitizer 1 A.