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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:
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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
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.

Test material

Reference
Name:
Unnamed
Type:
Constituent
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

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Induction
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
Challenge
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)

Results and discussion

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)

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
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 group
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

Applicant's summary and conclusion

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.