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Toxicological information

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:
1987
Reliability:
1 (reliable without restriction)

Data source

Reference
Title:
Unnamed
Year:
1987
Report date:
1987

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1981
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study available before entry into force of REACH

Test material

Constituent 1
Chemical structure
Reference substance name:
(ethyl-3-oxobutanoato-O'1,O'3)(2-dimethylaminoethanolato)(1-methoxypropan-2-olato)aluminium(III), dimerised
EC Number:
402-370-2
EC Name:
(ethyl-3-oxobutanoato-O'1,O'3)(2-dimethylaminoethanolato)(1-methoxypropan-2-olato)aluminium(III), dimerised
Cas Number:
149057-70-5
Molecular formula:
C14H28AlNO6
IUPAC Name:
octaaluminium(3+) octakis((2Z)-4-ethoxy-4-oxobut-2-en-2-olate) octakis(1-methoxypropan-2-olate) octakis(2-(dimethylamino)ethan-1-olate)
impurity 1
Chemical structure
Reference substance name:
1-methoxypropan-2-ol
EC Number:
203-539-1
EC Name:
1-methoxypropan-2-ol
Cas Number:
107-98-2
Molecular formula:
C4H10O2
IUPAC Name:
1-methoxypropan-2-ol
Test material form:
liquid
Details on test material:
purified with vacum distillation, analyzed by Gel permeation chromatography as stated in one of the study reports

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
arachis oil
Concentration / amount:
0.5%
Day(s)/duration:
7 days
Adequacy of induction:
highest technically applicable concentration used
Route:
intradermal
Vehicle:
other:
Remarks:
Freund's Complete Adjuvant plus arachis oil B.P. at the ratio of 1:1
Concentration / amount:
0.5%
Day(s)/duration:
7 days
Adequacy of induction:
highest technically applicable concentration used
Route:
epicutaneous, open
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Day(s)/duration:
7 days
Adequacy of induction:
highest technically applicable concentration used
Challenge
No.:
#20
Route:
epicutaneous, occlusive
Vehicle:
other: petroletum jully B.P.
Concentration / amount:
25% (challenge), 25% and 10% (re-challenge)
Day(s)/duration:
1
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 test and 10 controls
Details on study design:
a) Induction of the test animals
Induction of the Test Animals: The hair was removed from an area approximately 40 mm x 60 mm on the shoulder region of each animal with veterinary clippers and a row of three injections (0.1 ml each) was made on each side of the mid-line. The injections were:
i) Freund's Complete Adjuvant plus arachis oil B.P. in the ratio 1:1.
ii) a 0,5% (w/v) dilution of test material in arachis oil B.P.
iii) a 0,5% (w/v) dilution of test material in a 1:1 preparation of Freund's Complete Adjuvant plus arachis oil B.P.
One week later, the same area on the shoulder region used previously for intradermal injections was clipped again and treated with a topical appli­ cation of the undiluted test material. The undiluted test material (0.2 - 0.3 ml) was applied on filter paper (WHATMAN No. 4: approximate size 40 mm x 20 rrm) which was held in place by a strip of surgical adhesive tape (BLENDERM: approximate size 60 mm x 25 mm) and covered with an overlapping length of aluminium foil. The patch and foil were further secured by a trip of elastic adhesive bandage (ELASTOPLAST: approximate size 250 rrm x 35 11111) wound in a double layer around the torso of each animal. This occlusive dressing was kept in place for 48 hours. Erythematous reactions were quantified immediately following removal of the patches, using the D - 3 scale in section b.
One week later, the same area on the shoulder region used previously for intradermal injections was clipped again and treated with a topical appli­ cation of the undiluted test material. The undiluted test material (0.2 -
0.3 ml) was applied on filter paper (WHATMAN No. 4: approximate size 40 mm x 20 rrm) which was held in place by a strip of surgical adhesive tape (BLENDERM: approximate size 60 mm x 25 mm) and covered with an overlapping length of aluminium foil. The patch and foil were further secured by a trip of elastic adhesive bandage (ELASTOPLAST: approximate size 250 rrm x 35 11111) wound in a double layer around the torso of each animal. This occlusive dressing was kept in place for 48 hours. Erythematous reactions were quantified immediately following removal of the patches, using the D - 3 scale in section b.

Induction of the Control Animals:
Intradermal injections were administered using an identical procedure to that used for the test animals, except that the injections were:
i) Freund's Complete Adjuvant plus arachis oil B.P. in the ratio 1:1.
ii) arachis oil B.P.
iii) Freund's Complete Adjuvant plus arachis oil B.P. in the ratio 1:1.
The topical applications followed the same procedure as for the test animals except that nothing was applied to the filter paper. Skin reactions were quantified as for the test animals.

b) Challenge
Two weeks after the topical inductions, an area, approximately 50 - 70 mm x 50 mm on both flanks of each animal, was clipped free of hair with veterinary clippers.
A quantity of D.1 - D.2 ml of the test material formulation (25% w/w in petroleum jelly B.P.) was applied to the shorn rfght flank of each animal on a 20 mm x 20 mm square of filter paper (WHATMAN No. 4) which was held in place by a strip of surgica1 adhesive tape (BLEND£RM: approximate size 60 mm x 50 mm). The vehic1e alone was similarly applied to the left shorn flank. The patches were occluded with an overlapping length of aluminium foil and secured by a strip of elastic adhesive bandage (ELASTOPLAST: approximate size 250 mm x 75 mm) wound in a double layer around the torso of each animal.
After 24 hours, the dressing was carefully cut using blunt-tipped scissors, removed and discarded. The position of the treatment site was identified by using a black indelible marker-pen. After a further 24 and 48 hours, any erythematous reactions were quantified using the four-point scale shown and the number of positive responses recorded
Scale:
0 - no reaction
1 - scattered mild redness
2 - moderate and diffuse redness
3 - intense redness and swelling

c) Re-challenge
All test and control animals were re-challenged seven days later using concentrations of 25% (w/w) and 10% (w/w) in petroleum jelly B.P. on previously untreated areas of the shorn flank as detailed in the original challenge. The skin reactions were estimated 24 and 48 hours after removal of the dressing s as for the challenge. To classify the sensitisation response, the percentage of test animals that showed a more severe reaction at the test material challenge site than the
most severe reaction seen in the control animals, was compared with the following scale:
% of animals sensitised Classification of sensitisation potential
0 Non-sensitiser
> 0 - 8 Weak sensitiser
> 8 - 28 Mild sensitiser
> 28 - 64 Moderate sensitiser
> 64 - 80 Strong sensitiser
> 80 - 100 Extreme sensitiser

Challenge controls:
Induction of the Control Animals:
Intradermal injections were ad.ministered using an identical procedure to that used for the test animals, except that the injections were:
i) Freund's Complete Adjuvant plus arachis oil B.P. in the ratio 1:1.
ii) arachis oil B.P.
iii) Freund's Complete Adjuvant plus arachis oil B.P. in the ratio 1:1. The topical applications followed the same procedure as for the test animals except that nothing was applied to the filter paper. Skin reactions were quantified as for the test animals.
Positive control substance(s):
yes
Remarks:
Formaldehyde (40% aqueous solution)

Results and discussion

Positive control results:
The strain used in these laboratories has been shown to produce a satisfactory sensitisation response using a known positive sensitiser

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: initial challenge
Hours after challenge:
24
Group:
test chemical
Dose level:
25% in petrolatum jelly
No. with + reactions:
13
Total no. in group:
20
Clinical observations:
scale 0: 7 animals, scale 1: 11 animals, scale 2: 2 animals, scale 3: 0 animals
Remarks on result:
no indication of skin sensitisation
Reading:
other: initial challenge
Hours after challenge:
48
Group:
test chemical
Dose level:
25% in petrolatum jelly
No. with + reactions:
5
Total no. in group:
20
Clinical observations:
scale 0: 15 animals, scale 1: 4, scale 2: 1 scale 3: 0
Remarks on result:
no indication of skin sensitisation
Reading:
other: initial challenge
Hours after challenge:
24
Group:
positive control
Dose level:
25%
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
scale 0: 2 animals, scale 1: 7 animals, scale 2: 1 animal
Remarks on result:
no indication of skin sensitisation
Remarks:
control - test material
Reading:
other: initial challenge
Hours after challenge:
48
Group:
positive control
Dose level:
25%
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
scale 0: 8 animals, scale 1: 2 animals
Remarks on result:
no indication of skin sensitisation
Remarks:
freud's adjuvant and arachis oil
Reading:
other: initial challenge
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
vehicule
Reading:
other: iniitla challenge
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
vehicule
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
12
Total no. in group:
20
Clinical observations:
scale 0:8, scale 1: 12
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
scale 0: 18, scale 1: 2
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
scale 0:7 animals, scale 1:3 animals
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
positive control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
positive control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
48
Group:
positive control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

Skin response scale:

0 - no reaction

1- scattered mild redness

2- moderate and diffuse redness

3- intense redness and swelling

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test material, therefore, produced a 0% (0/20) sensitisation rate and therefore was classified as a NON-SENSITIZER to guinea pig skin.
Executive summary:

In a guinea pigs OECD 426 test, the test material tested at 10% and 25% in challenge phase produced a 0% (0/20) sensitisation rate and therefore was classified as a NON-SENSITIZER to guinea pig skin.