Tetra(isobutyl)thioperoxydicarbamic acid

Endpoint summary

Description of key information

Skin sensitisation: Not sensitising (Similar to OECD 406, Buehler test, GLP)

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:

01-02-1996 to 06-03-1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The guideline recommends 20 animals in the test group and 10 in the control group. As there was only one reaction (slight patchy erythema) in 1 animal of 10 animals in the test group, it is not expected that the number of the test animals will affect the conclusion that the substance is not a skin sensitiser. The results of the DNCB positive control study demonstrated that a valid test was performed and indicated that the test design would detect potential contact sensitisers.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

An existing in vivo skin sensitisation study in guinea pigs was available.

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: R.T. Vanderbilt Company, Inc, 30 Winfield Street, PO Box 5150, Norwalk, CT 06856-5150; 5K18-1

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

Species:

guinea pig

Strain:

other: Hartley-derived albino

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan
- Females (if applicable) nulliparous and non-pregnant: [yes/no/not specified]
- Microbiological status of animals, when known:
- Age at study initiation: Young adult
- Weight at study initiation: 300-500g
- Housing: Suspended stainless steel cages
- Diet: PMI Certified Guinea Pig Chow #5026 (Purina Mills Inc) ad libitum
- Water: Municipal tap water ad libitum
- Acclimation period: five days


ENVIRONMENTAL CONDITIONS
- Temperature: 64-71F
- Humidity (%): 27-69
- Air changes (per hr): 10-15 changes
- Photoperiod (hrs dark / hrs light): 12 hour light/21 hour dark

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.40 g (100%)

Day(s)/duration:

7

Adequacy of induction:

highest technically applicable concentration used

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.4g (100%)

Day(s)/duration:

6 hours

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

5 males
5 females

Details on study design:

RANGE FINDING TESTS: ON the day prior to dose administration, 4 induction range-finding guinea pigs were weighed and the hair removed from the right and left side of the animals. On the following daty, 4 concentrations of the test article (25, 50, 75 and 100%) were prepared and applied. The chambers were applied and the test site occlusively covered. Approximately 6 hours after application, the occlusive dressing was removed and the test sites were wiped with distilled water to remove test article residue and the animals returned to their cages. Mortality, clinical observations and body weights were recorded. The test sites were graded for irritation at 24 and 48 hours following chamber application. Following the 48 hour scoring interval, all animals were euthanised; gross necropsy was not performed.
The results of the topical range-finding study indicated that a test article concentration of 100% was considered appropriate for induction (Appendix B).

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 7 days
- Test groups: 0.4g of 100% TiBTD to 5 males/females
- Control group: 0.3 mL of 0.1% DNCB (Lot No. 12423MZ) to 5 males/females was used as the positive control

B. CHALLENGE EXPOSURE
- No. of exposures: Once
- Day(s) of challenge: Approximately 6 hours after application, the occlusive dressing was removed and the test sites were wiped with distilled water to remove test article residue and the animals returned to their cages.
- Test groups: 0.4g of 100% TiBTD to 5 males/females
- Control group: 0.3 mL of 0.1% and 0.05% DNCB (Lot No. 12423MZ) to 5 males/females was used as the positive control
- Evaluation (hr after challenge): The test sites were graded for irritation at 24 and 48 hours following chamber application (Protocol Appendix B).

Mortality, clinical observations and body weights were recorded. Following the 48 hour scoring interval, all animals were euthanised; gross necropsy was not performed.

Positive control substance(s):

yes

Remarks:

1-Chloro 2,4 nitrobenzene (DNCB)

Positive control results:

Following challenge with DNCB, 10/10 DNCB test animals were noted to have a substantially stronger dermal response than was observed in the corresponding DNCB control animals. Group mean dermal scores were also noted to be higher in the DNCB test animals as compared to those of the DNCB control animals (Tables 2 and 4)

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100%

No. with + reactions:

1

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100%

No. with + reactions:

1

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

0.05 and 0.1%

No. with + reactions:

10

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

0.05 and 0.1%

No. with + reactions:

10

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study, TiBTD is not considered to be a contact sensitiser in guinea pigs. The results of the DNCB positive control study demonstrated that a valid test was performed and indicated that the test design would detect potential contact sensitisers.

Executive summary:

In a dermal sensitization study (3248.34) with TiBTD, young adult Hartley-derived albino guinea pigs (5/sex/dose) were tested using the Buehler test method. For induction, 100% TiBTD (epicutaneous occlusive) and was used. For challenge, 100% TiBTD (epicutaneous occlusive) was used. The evaluation of skin reactions after challenge was carried out at 24 and 48 hrs. The positive control was 1-Chloro 2,4 nitrobenzene (DNCB).

DNCB caused a positive skin reaction (moderate, confluent erythema to severe erythema with or without edema) in 10 of 10 animals. TiBTD caused a positive skin reaction (slight patchy erythema) in 1 of 10 animals. There were no reactions in the control group. The exposed animals showed no other negative clinical symptoms throughout the experiment. The body weight of animals increased during the study and it was not affected by the treatment. In this study, TiBTD is not a dermal sensitizer.

This dermal sensitization study is acceptable and satisfies the guideline requirement for an OECD 406 study. The guideline recommends 20 animals in the test group and 10 in the control group. As there was only one reaction (slight patchy erythema) in 1 animal of 10 animals in the test group, it is not expected that the number of the test animals will affect the conclusion that the substance is not a skin sensitiser. The results of the DNCB positive control study demonstrated that a valid test was performed and indicated that the test design would detect potential contact sensitisers.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

There is one skin sensitisation test in guinea pigs available.

In a dermal sensitization study (similar to OECD 406/GLP) with TiBTD, young adult Hartley-derived albino guinea pigs (5/sex/dose) were tested using the Buehler test method. For induction, 100% TiBTD (epicutaneous occlusive) and was used. For challenge, 100% TiBTD (epicutaneous occlusive) was used. The evaluation of skin reactions after challenge was carried out at 24 and 48 hrs. The positive control was 1-Chloro 2,4 nitrobenzene (DNCB). DNCB caused a positive skin reaction (moderate, confluent erythema to severe erythema with or without edema) in 10 of 10 animals. TiBTD caused a positive skin reaction (slight patchy erythema) in 1 of 10 animals. There were no reactions in the control group. The exposed animals showed no other negative clinical symptoms throughout the experiment. The body weight of animals increased during the study and it was not affected by the treatment. In this study, TiBTD is not a dermal sensitizer.

The guideline recommends 20 animals in the test group and 10 in the control group. As there was only one reaction (slight patchy erythema) in 1 animal of 10 animals in the test group, it is not expected that the number of the test animals will affect the conclusion that the substance is not a skin sensitiser. The results of the DNCB positive control study demonstrated that a valid test was performed and indicated that the test design would detect potential contact sensitisers.

The results from this study are suitable to use in the human health hazard assessment.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available information in the dossier, the substance TiBTD (CAS No3064-73-1) does not need to be classified  for skin sensitisation when the criteria outlined in Annex I of 1272/2008/EC and Annex I of 286/2011/EC are applied.