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Description of key information

Polysulfide, di-tert-butyl was a skin sensitizer to guinea pigs using the maximization test (OECD TG 406) following induction with 25% intracutaneous and 100% epicutaneous solutions and challenge with a 100% solution.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
A positive control was not tested but the test substance was a skin sensitizer in this test.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was performed before the publication of the REACH regulation
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Lebeau breeding centre (78950 Gambais, France)
- Age at study initiation: no data
- Weight at study initiation: 328 +/-18 g for the males and 314 +/- 10 g for the females
- Housing: individually in polycarbonate cages
- Diet (e.g. ad libitum): Guinea-pigs sustenance ref. 106 (UAR, 91360 Villemoisson/Orge, France)
- Water (e.g. ad libitum): filtered tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/- 20
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
25%
Day(s)/duration:
D1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Day(s)/duration:
D8
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
Day(s)/duration:
D22
No. of animals per dose:
Thirty guinea-pigs (15 males and 15 females) were allocated to 2 groups: a control group (5 males and 5 females) and a treated group (10 males and 10 females)
Details on study design:
The sensitization potential of TPS 44 was evaluated after a 10-day induction period during which the animals were treated with the vehicle (control group) or the test substance (treated group). On day 1, in the presence of Freund's adjuvant, 0.1 ml of the test substance was administered by intradermal route at a concentration of 25% in an injectable isotonic solution of 0.9% NaCl. On day 8, 0.5 ml of the test substance in its original form was applied by cutaneous route. After a period of 12 days without treatment, a challenge cutaneous application of 0.5 ml of the vehicle (left flank) and 0.5 ml of the test substance in its original form (right flank) were then performed on all animals. The substances were prepared on a dry compress, then applied to the skin and held in place for 24 hours by means of an occlusive dressing. The cutaneous reactions were then evaluated at the challenge application site, 24 and 48 hours after removal of the dressing. No histological examination was performed on the cutaneous samples.
Positive control substance(s):
no
Positive control results:
Not tested but the test substance was a skin sensitizer in this test.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
14
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
9
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Group:
positive control
Remarks on result:
other: Not tested but the test substance was a skin sensitizer in this test.
During the study, no clinical signs were observed and no
death occurred. The body weight of the animals of the
treated group was unaffected when compared to that of the
control group.

After the challenge application of the test substance, no
cutaneous reactions were observed in the animals of the
control group. A positive response characterised by a
well-defined erythema (score of 2) was observed on the right
flank of 9 treated animals after 24 and 48 hours. No oedema
was noted. The reactions noted in 10 animals (very slight or
well-defined erythema after 24 hours and very slight
erythema after 48 hours) were considered to be inconclusive
evidence of well-defined sensitization and were considered
to be due to a slight sensitization effect.
Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
TPS 44 induced a positive sensitization reaction in 9 out of 20 guinea-pigs (45%).
Executive summary:

The sensitization potential of di-tert-butyl polysulfides (TPS 44) was evaluated in guinea-pigs by intradermal injection and cutaneous application, according to the maximization method of Magnusson and Kligman, the O.E.C.D. Guideline No. 406 and GLP. Thirty guinea-pigs (15 males and 15 females) were allocated to 2 groups: a control group (5 males and 5 females) and a treated group (10 males and 10 females). The sensitization potential of TPS 44 was evaluated after a 10-day induction period during which the animals were treated with the vehicle (control group) or the test substance (treated group). On day 1, in the presence of Freund's adjuvant, 0.1 ml of the test substance was administered by intradermal route at a concentration of 25% in an injectable isotonic solution of 0.9% NaCl. On day 8, 0.5 ml of the test substance in its original form was applied by cutaneous route. After a period of 12 days without treatment, a challenge cutaneous application of 0.5 ml of the vehicle (left flank) and 0.5 ml of the test substance in its original form (right flank) were then performed on all animals. The substances were prepared on a dry compress, then applied to the skin and held in place for 24 hours by means of an occlusive dressing. The cutaneous reactions were then evaluated at the challenge application site, 24 and 48 hours after removal of the dressing. No histological examination was performed on the cutaneous samples. During the study, no clinical signs were observed and no death occurred. The body weight of the animals of the treated group was unaffected when compared to that of the control group. After the challenge application of TPS 44, no cutaneous reactions were observed in the animals of the control group. A positive response characterised by a well-defined erythema (score of 2) was observed on the right flank of 9 treated animals after 24 and 48 hours. No oedema was noted. The reactions noted in 10 animals (very slight or well-defined erythema after 24 hours and very slight erythema after 48 hours) were considered to be inconclusive evidence of well-defined sensitization and were considered to be due to a slight sensitization effect. TPS 44 induced a positive sensitization reaction in 9 out of 20 guinea-pigs (45%).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

The sensitization potential of polysulfides, di-tert-butyl was evaluated in guinea-pigs by intradermal injection and cutaneous application, according to the maximization method of Magnusson and Kligman (1), the OECD Guideline No. 406 and compliance with GLP (Clouzeau, 1992d). Thirty guinea-pigs (15 males and 15 females) were allocated to 2 groups: a control group (5 males and 5 females) and a treated group (10 males and 10 females). The sensitization potential of polysulfides, di-tert-butyl was evaluated after a 10-day induction period during which the animals were treated with the vehicle (control group) or the test substance (treated group). On day 1, in the presence of Freund's adjuvant, 0.1 ml of the test substance was administered by intradermal route at a concentration of 25% in an injectable isotonic solution of 0.9% NaCl. On day 8, 0.5 ml of the test substance in its original form was applied by cutaneous route. After a period of 12 days without treatment, a challenge cutaneous application of 0.5 ml of the vehicle (left flank) and 0.5 ml of the test substance in its original form (right flank) were then performed on ail animals. The substances were prepared on a dry compress, then applied to the skin and held in place for 24 hours by means of an occlusive dressing. The cutaneous reactions were then evaluated at the challenge application site, 24 and 48 hours after removal of the dressing. No histological examination was performed on the cutaneous samples. During the study, no clinical signs were observed and no death occurred. The body weight of the animais of the treated group was unaffected when compared to that of the control group. After the challenge application of polysulfides, di-tert-butyl , no cutaneous reactions were observed in the animals of the control group. A positive response characterised by a well-defined erythema (score of 2) was observed on the right flank of 9 treated animals after 24 and 48 hours. No oedema was noted. The reactions noted in 10 animals (very slight or well-defined erythema after 24 hours and very slight erythema after 48 hours) were considered to be inconclusive evidence of well-defined sensitization and were considered to be due to a slight sensitization effect. Polysulfides, di-tert-butyl induced a positive sensitization reaction in 9 out of 20 guinea-pigs (45%).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to the skin sensitizing potential observed, polysulfides, di-tert-butyl is classified Category 1B (Warning; H317: May cause an allergic skin reaction) under the EU CLP regulation.