Registration Dossier

Administrative data

Description of key information

One key study in guinea pigs was identified to evaluate the skin sensitising potential of di-tert-nonyl polysulfide, which was conducted according to OECD TG 406 and in compliance with GLP. The study concluded the test material to be not sensitising to skin (Manciaux, 2002).

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:
2001-12-28 to 2002-02-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
Cited as Directive 96/54/EC, B.6
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
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.
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
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.
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
Positive control results:
no data
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
1% challenge
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No cutaneous reactions were noted
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1% challenge
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No cutaneous reactions were noted
Remarks on result:
no indication of skin sensitisation
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:
no indication of skin sensitisation
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:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
20 % (w/w)
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Oedema
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
20 % (w/w)
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Oedema
Remarks on result:
positive indication of skin sensitisation

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

Interpretation of results:
GHS criteria not met
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

One key study in guinea pigs was identified to evaluate the skin sensitising potential of di-tert-nonyl polysulfide.

 

In a key skin sensitization test (Manciaux, 2002; Klimisch score = 1), 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.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In a dermal sensitisation study, di-tert-nonyl polysulfide was not observed to be a skin sensitiser in guinea pigs. Therefore, di-tert-nonyl polysulfide does not meet the criteria for classification as a dermal sensitiser under CLP Regulation (EC) No 1272/2008.