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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented. Data is suitable for read-across.

Data source

Reference
Reference Type:
publication
Title:
Evaluation of skin sensitization potential of nickel, chromium, titanium and zirconium salts using guinea-pigs and mice
Author:
Ikarashi Y, Momma J, Tsuchiya T, Nakamura A
Year:
1996
Bibliographic source:
Biomaterials 17: 2103-2108

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
(no data on test material purity, no range finding test was carried out prior the sensitisation test to determine the minimal irritating and maximal non-irritating concentration)
Principles of method if other than guideline:
The sensitisation potential of titanium tetrachloride was evaluated in the guinea pig maximization test.
GLP compliance:
not specified
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Titanium tetrachloride, TiCl4
- Analytical purity: The test substance was obtained from Wako Pure Chemical Industries, no data on purity

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Japan SLC Inc.
- Weight at study initiation: 350-400 g

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: saline or ethanol
Concentration / amount:
intradermal injection (induction): 0 and 1%; topical application (induction): 0 and 1%; challenge: 0, 2 and 5 %
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: saline or ethanol
Concentration / amount:
intradermal injection (induction): 0 and 1%; topical application (induction): 0 and 1%; challenge: 0, 2 and 5 %
No. of animals per dose:
Controls: 5 animals
Treated: 10 animals
Details on study design:
In this study two independent tests were carried out to determine the sensitisation potential of the test substance.
The GPMT was performed according to the procedure described by Magnusson and Kligman (1969) with some modification. Preliminary irritation tests were carried out to determine the suitable concentrations for induction and challenge. Test guinea pigs received a series of 6 intradermal injections of the test chemical at 1% * in FCA emulsion into the shoulder region to induce sensitization. Seven days later, the animals received a 48 h occluded patch containing the chemical at the same site to boost sensitization.
The animals were challenged on flank with 20 µl of various concentrations of test chemical on the 14 days following the induction. Skin reaction was determined by visual assessment 48 h after challenge.
The intensity of the reaction was scored according to the criteria: 0 = no visible change, 1 = slight or discrete erythema, 2 = moderate and confluent erythema, 3 = intense erythema and swelling. The sensitization rate and mean skin response were also calculated. Rechallenge was performed on the 7 days after the first challenge.

* To determine the minimum induction concentration of the test chemical, one needs many animals. Therefore, an injection concentration to 1% for all chemicals was set up, and the challenge concentration was changed. In the GPMT, the minimum challenge concentration of the test substance to induce a skin response following 1% injection was 2%.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
Test A: 5 %
No. with + reactions:
0
Total no. in group:
3
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Test A: 5 %. No with. + reactions: 0.0. Total no. in groups: 3.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
Test A: 0 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: Test A: 0 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
Test A: 1 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: Test A: 1 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
Test A: 5 %
No. with + reactions:
1
Total no. in group:
5
Clinical observations:
1 of 5 animals showed weak skin response
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: Test A: 5 %. No with. + reactions: 1.0. Total no. in groups: 5.0. Clinical observations: 1 of 5 animals showed weak skin response.
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
Test A: 2 %
No. with + reactions:
3
Total no. in group:
5
Clinical observations:
3 of 5 animals responded after rechallenge (60 %) with stronger intensity
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: Test A: 2 %. No with. + reactions: 3.0. Total no. in groups: 5.0. Clinical observations: 3 of 5 animals responded after rechallenge (60 %) with stronger intensity.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
Test B: 2 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Test B: 2 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
Test B: 5 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Test B: 5 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
Test B: 0 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: Test B: 0 %. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
Test B: 2 %
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: Test B: 2 %. No with. + reactions: 1.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
Test B: 5 %
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
With regard to the results from test 1, the test substance was retested with more animals. Five of 10 (50 %) showed skin reactions by challenge.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: Test B: 5 %. No with. + reactions: 5.0. Total no. in groups: 10.0. Clinical observations: With regard to the results from test 1, the test substance was retested with more animals. Five of 10 (50 %) showed skin reactions by challenge. .

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information