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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:
2001-12-28 to 2002-02-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study is classified as reliable without restriction because it is GLP compliant and follows OECD Guideline 406.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
Cited as Directive 96/54/EC, B.6
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Remarks:
OECD GLP ENV/MC/CHEM(98)17; Commission Directive 1999/11/EC; Ministere de l'Economie, Des Finances et de l'Industrie
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was performed before the implementation of the REACH Regulation.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test compound: TPS 37 LS
Source: Atofina SA
Batch: 30-01-GF
Total sulfur: 36.75% (w/w)
Mercaptans: 1 ppm

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
-sex: male and nulliparous and non-pregnant female guinea pigs.
-justification for species choice: species generally accepted by regulatory authorities for this type of study. The strain used has been shown to produce a satisfactory sensitization response using known sensitizers.
- source: Charles River Laboratories, Saint-Aubin-lès-Elbeuf, France.
- age: 1-3 months
- weight: 422 ± 17 g for the males and 414 ± 21 g for the females.
- acclimation: at least 5 days before the beginning of the study
- food: ad libitum, 106 pelleted diet
- water: ad libitum

ENVIRONMENTAL CONDITIONS
- housing: 48 cm x 27 cm x 20 cm
- temperature: 22 ± 2°C
- relative humidity: 30 to 70%
- light/dark cycle: 12 h/12 h
-ventilation: approximately 12 cycles/hour of filtered, non-recycled air

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: intrademal = corn oil; epicutaneous = acetone
Concentration / amount:
Induction (treated group)
Intradermal injections (day 1): TPS 37 LS at the concentration of 25% (w/w) in corn oil,
Topical application (day 8): TPS 37 LS at the concentration of 50% (w/w) in acetone.

Challenge (all groups)
Topical application (day 22): TPS 37 LS at the concentration of 1% (w/w) in acetone.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: intrademal = corn oil; epicutaneous = acetone
Concentration / amount:
Induction (treated group)
Intradermal injections (day 1): TPS 37 LS at the concentration of 25% (w/w) in corn oil,
Topical application (day 8): TPS 37 LS at the concentration of 50% (w/w) in acetone.

Challenge (all groups)
Topical application (day 22): TPS 37 LS at the concentration of 1% (w/w) in acetone.
No. of animals per dose:
5/sex for control; 10/sex for treated group
Details on study design:
1st application: Induction 25 % intracutaneous
2nd application: Induction 50 % occlusive epicutaneous
3rd application: Challenge 1 % occlusive epicutaneous
Challenge controls:
left flank - vehicle only (acetone)
Positive control substance(s):
no

Results and discussion

Positive control results:
no data

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1% challenge
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No cutaneous reactions were noted
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1% challenge. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No cutaneous reactions were noted.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1% challenge
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No cutaneous reactions were noted
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1% challenge. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No cutaneous reactions were noted.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
no test substance
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No cutaneous reactions were noted
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: no test substance. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No cutaneous reactions were noted.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
no test substance
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No cutaneous reactions were noted
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: no test substance. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No cutaneous reactions were noted.

Any other information on results incl. tables

No clinical signs and no deaths related to treatment were noted during the study. No cutaneous reactions were observed after the challenge application.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
According to the maximization method of Magnusson and Kligman, the test item TPS 37 LS at the concentration of 1% does not induce delayed contact hypersensitivity in guinea pigs.
Executive summary:

In a skin sensitization test, male and female Hartley guinea pigs (10/sex) were exposed to di-tert-nonyl polysulfide (TPS 37 LS; CAS # 68425-16-1). On day 1 of the induction phase, all animals in the treatment group were administered the following 3 pairs of intradermal injections in the intrascapular region: (1) Freund’s complete adjuvant (FCA) 50% v/v in 0.9% NaCl; (2) TPS 37 LS (25% w/w in corn oil; and (3) TPS 37 LS (25% w/w in corn oil) in a 50% v/v mixture of FCA and 0.9% NaCl. Animals in the control group were administered corn oil using a dosing regimen identical to the one described above. On day 8 of the induction phase, animals in the treatment group were topically administered TPS 37 LS (at the same site) at a concentration of 50% (w/w) in acetone while animals in the control group were topically administered the vehicle control acetone. The application sites were subsequently covered with occlusive dressing for a period of 48 hours.On day 22, all animals of the test and control group were challenged by a cutaneous application of TPS 37 LS (1% w/w in acetone) to the right flank. The left flank served as control and received the vehicle only. Subsequently, the test material and vehicle control were maintained under an occlusive dressing for a period of 24 hours and skin reactions were evaluated approximately 24 and 48 hours after removal of the dressing.

No mortality or signs of adverse clinical toxicity were observed at challenge or through the study period. No positive reactions were noted for any of the test (0/20) or control animals (0/10) at 24 and 48 hours. Based on these results, TPS 37 LS was not found to be sensitising in the guinea pig maximisation test.

This study received a Klimisch Score of 1 and was classified as reliable without restriction because it is GLP compliant and follows OECD Guideline 406.