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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:
11 December 1998 to 08 January 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished report, accepted without restriction

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
Also according to:
* "Biological evaluation of medical devices"
* ISO 10993-1: 1997, "Evaluation and testing"
* ISO 10993-10: 1995, (6.3) "Tests for irritation and sensitization"
* ISO 10993-12: 1996, "Sample preparation and reference material"
* DIN EN 30993-1: 1994 and DIN EN ISO 7405:1998 (5.2.2e) "Preclinical evaluation of biocompatibility of medical devices used in dentistry - Test methods"
GLP compliance:
yes (incl. QA statement)
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): Ectectior Vision, dental alloy for the ceramic fused-to-metal technic
- Physical state: solid
- Composition of test material, percentage of components: Au 98.2%, Ti 1.7%, Ir 0.1%
- Lot/batch No.: 2974
- Expiration date of the lot/batch: none
- Stability under test conditions: Unlimited stable
- Storage condition of test material: at room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelman GmbH, D-33178 Borchen
- Age at study initiation: Not reported
- Weight at study initiation: 301 - 316 g
- Housing: Terluran cages on Altromin saw fiber bedding. Max caging group size: 10 animals.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): not reported
- Acclimation period: Under test conditions for one week.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 55 ± 10%
- Air changes (per hr): at least 10x / hour
- Photoperiod (hrs dark / hrs light): Artificial lighting, 12 hours light, 12 hours dark


IN-LIFE DATES: Not reported

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Concentration / amount:
Three pairs of 0.1 ml injections were administered, with 0, 100 and 50% concentration of test item in Freund's adjuvant complete. Topic application was a solid specimen of test item, dimensions 15 x 30 x 1 mm.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
Three pairs of 0.1 ml injections were administered, with 0, 100 and 50% concentration of test item in Freund's adjuvant complete. Topic application was a solid specimen of test item, dimensions 15 x 30 x 1 mm.
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS: Not reported

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 interdermal, 1 topical
- Exposure period: Interdermal injections: Day 0, Topical: 48 hour patch (days 7 & 8)
- Test groups: 1
- Control group: 1
- Site: Shoulder region
- Frequency of applications: No repetition
- Duration: Topical: 48 hour patch
- Concentrations: Three pairs of 0.1 ml injections were administered, with 0, 100 and 50% concentration of test item in Freund's adjuvant complete. Topic application was a solid specimen of test item, dimensions 15 x 30 x 1 mm.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 20
- Exposure period: 24 hours
- Test groups: 1
- Control group: 1
- Site: Left flank
- Concentrations: Solid specimen of test item, dimensions 15 x 30 x 1 mm.
- Evaluation (hr after challenge): 24, 48 & 72 hours
Challenge controls:
5 animals were inducted with injections lacking the test item.
Positive control substance(s):
yes
Remarks:
Mercaptobenzothiazole

Results and discussion

Positive control results:
see table 1

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test chemical
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Any other information on results incl. tables

Table 1 - Frequency of Sensitization in Positive Control Animals

  Erythema Grade Oedema Grade  
Time after challenge treatment (hours) E0 E1 E2 E3 E4 O0 O1 O2 O3 O4 %
24 4 4 2     10         60
48 4 3 3     10         60
72 8 2       10         20

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
A Guinea-Pig Maximisation test showed that gold is not a skin sensitizer.
Executive summary:

A GLP-compliant, OECD Guideline (406) Guinea-Pig Maximisation test showed that gold is not a skin sensitizer.