Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
October 23, 1978 - January 12, 1979
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Non-GLP study that predates current guideline. There is no positive control and no use of Freund's complete adjuvant.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Principles of method if other than guideline:
Two days after the primary irritation test (see chapter 7.3.1 Skin irritation/corrosion.weight_of_evidence.001), induction phase for sensitisation test was started. A series of four intradermal injections of 0.1ml of a 1% test substance solution in acetone/dimethyl phthalate (DMP) 1:9 was given to ten guinea pigs, one each week over three-week period. Following two-week rest period, the test animals were challenged for sensitization by applying 0.05ml of a 50% and 5% suspension of test material in DMP on shaved shoulder skin. At the same time a control group of 10 previously unexposed guinea pigs received similair applications to provide a direct comparison of the challenge reactions.
The skin at the challenge site was evaluated for irritation at 24 and 48 hours after application. Sensitization was defined as a significant score increase at challenge over the response expected from the same amount applied initially or on the concurrent controls.

GLP compliance:
not specified
Type of study:
intracutaneous test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Titanic Acid, tetrakis(2-ethylhexyl) ester
Tyzor TOT Haskell No. 12,676
Purity 95%

In vivo test system

Test animals

Species:
guinea pig
Strain:
not specified
Details on test animals and environmental conditions:
Albino guinea pigs were used. Initial average weight of animals was 451g and final average weight was 696g. No details on environmental conditions were reported.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: acetone/dimethyl phthalate for the induction phase and dimethyl phthalate for the challenge phase
Concentration / amount:
1.0% solution of the test item in acetone/dimethyl phthalate was administered in the induction phase and a 50% or 5% suspension of the test item in dimethyl phthalate was applied at the challenge.
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
other: acetone/dimethyl phthalate for the induction phase and dimethyl phthalate for the challenge phase
Concentration / amount:
1.0% solution of the test item in acetone/dimethyl phthalate was administered in the induction phase and a 50% or 5% suspension of the test item in dimethyl phthalate was applied at the challenge.
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS: a skin irritation study was initially conducted (this is reported in IUCLID chapter 7.3.1).

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 4
- Exposure period: 4 weeks
- Test groups: 10 per group
- Control group: 10 animals
- Site: intradermal
- Frequency of applications: at weekly intervals
- Duration: for 4 weeks
- Concentrations: 1.0% in acetone/ dimethyl phthalate

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: following a 2 week rest period after the last induction treatment
- Exposure period: test item was lightly rubbed into skin. No information was supplied regarding duration of exposure.
- Test groups: 2
- Control group: yes
- Site: shoulder skin
- Concentrations: 50% and 5% in dimethyl phthalate
- Evaluation (hr after challenge): 24 and 48 hours

CONTROLS
At the challenge test, 10 unexposed guinea pigs of the same age received identical topical applications to the 50% and 5% test item groups. Therefore these animals had not been treated during the induction phase but were similarly treated during the challenge phase.
Challenge controls:
10 animals at 50% and 10 animals at 5% test item in vehicle.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50% in vehicle
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
2++, 6+, 2 negative for sensitisation
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% in vehicle. No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: 2++, 6+, 2 negative for sensitisation.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5% in vehicle
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
3+, 7 negative for sensitisation
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5% in vehicle. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: 3+, 7 negative for sensitisation.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50% in vehicle
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
1++,9+, 0 negative for sensitisation
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50% in vehicle. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: 1++,9+, 0 negative for sensitisation.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5% in vehicle
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
2+, 8 negative for sensitisation
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5% in vehicle. No with. + reactions: 2.0. Total no. in groups: 10.0. Clinical observations: 2+, 8 negative for sensitisation.
Reading:
1st reading
Hours after challenge:
24
Group:
other: challenge control for 50%
Dose level:
50% in vehicle
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
7+, 3 negative for sensitisation
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: challenge control for 50%. Dose level: 50% in vehicle. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: 7+, 3 negative for sensitisation.
Reading:
1st reading
Hours after challenge:
24
Group:
other: challenge control for 5%
Dose level:
5% in vehicle
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
1+, 9 negative for sensitisation
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: challenge control for 5%. Dose level: 5% in vehicle. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: 1+, 9 negative for sensitisation.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: challenge control for 50%
Dose level:
50% in vehicle
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
7+, 3 negative for sensitisation
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: challenge control for 50%. Dose level: 50% in vehicle. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: 7+, 3 negative for sensitisation.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: challenge control for 5%
Dose level:
5% in vehicle
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
1+, 9 negative for irritation
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: challenge control for 5%. Dose level: 5% in vehicle. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: 1+, 9 negative for irritation.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The potential sensitisation properties of titanium tetrakis(2-ethylhexanolate) were tested using primary sensitization test on guinea pigs. Based on the study results test substance is considered as not skin sensitizer. No guideline was followed in this study.
Executive summary:

The test substance was administrated 1% solution (vol/vol) in acetone/DMP 1:9 in a series of four sacral intradermal injections (10 animals). At the time of challenge 0.05ml 5% and 50% test substance (vol/vol) in DMP was applied and lightly rubbed to the shaved intact shoulder skin. A control group of 10 previously unexposed guinea pigs received similair applications at the same time to provide a direct comparison of the challenge reactions. At challenge no sensitization response was observed.

This study was regarded not reliable since the study report contains insufficient details on study methods and results. This study does not satisfy the guideline requirements for the sensitization study, but the result is used as a weight of evidence in hazard assessment.