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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:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study and GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: ISO 10993-10, Biological Evaluation of Medical Devices Part 10: Test for Irritation and Skin Sensitization
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
XFlex is a formulation of 94.5% 1-methylheptyl cyanoacrylate with plasticisers and accelerant.
Extracts of the polymerized adhesive were investigated (see below).

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: USP 0.9 % NaCl, Cottonseed Oil
Concentration / amount:
positive control: 0.1 %;
extracts of test articles were used neat
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: USP 0.9 % NaCl, Cottonseed Oil
Concentration / amount:
positive control: 0.1 %;
extracts of test articles were used neat
No. of animals per dose:
10 animals per extrakt (Test item)
5 animals per extrakt (Negative Controls)
5 animals per extrakt (Positive Contols)
Positive control substance(s):
yes
Remarks:
Dinitrochlorobenzene (DNCB)

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
NaCl extract
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: NaCl extract. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
NaCl extract
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: NaCl extract. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
NaCl extract
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading:
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
cottonseed oil extract
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: cottonseed oil extract. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
cottonseed oil extract
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: cottonseed oil extract. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test group
Dose level:
cottonseed oil extract
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading:
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
vehicle (NaCl, Cottonseed oil)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: vehicle (NaCl, Cottonseed oil). No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle (NaCl, Cottonseed oil)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: vehicle (NaCl, Cottonseed oil). No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
vehicle (NaCl, Cottonseed oil)
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading:
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1% DNCB
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.1% DNCB. No with. + reactions: 5.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1% DNCB
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.1% DNCB. No with. + reactions: 5.0. Total no. in groups: 5.0.
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
positive control
Dose level:
0.1% DNCB
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
other: Reading:

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The USP 0.9 % Sodium Chloride for Injection (NaCl) and Cottonseed Oil extracts of the test article, XFLEX TISSUE ADHESIVE, elicided no reaction at the challenge (0 % sensitization), following an induction phase. Therefore, as defined by the scoring system of Kligman, this is a Grade I reaction and the test article is classified as having weak allergic potential. Based on the criteria of the protocol, a Grade I sensitisation rate is not considered significant and the test article meets the requirements of the ISO 10993-10 guidelines.
Executive summary:

The USP 0.9 % Sodium Chloride for Injection (NaCl) and Cottonseed Oil (CSO) extracts of the test article, XFLEX TISSUE ADHESIVE, elicited no reaction at the challenge (0% sensitization), following an induction phase, Therefore, as defined by the scoring system of Kligman, this is a Grade I reaction and the test article is classified as having weak allergenic potential. Based on the criteria of the protocol, a Grade I sensitization rate is not considered significant and the test article meets the requirements of the ISO 10993 -10 guidelines.