Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001-04-09 to 2001-06-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: A human Repeat Insult Patch Test was performed in 2001 in accordance with Good Clinical Practices.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001
Reference Type:
publication
Title:
Unnamed
Year:
2003

Materials and methods

Principles of method if other than guideline:
The Modified Draize Procedure is used as a predictive test for contact sensitization in humans. The procedure involves the application of a discontinuous series of multiple occlusive patches to human skin over a three week induction period. Induction is followed by an approximate two week rest period. Challenge consists of a single application to naive skin.
GLP compliance:
yes
Remarks:
Good Clinical Practice
Type of study:
patch test
Justification for non-LLNA method:
The study was conducted before the requirement to use the LLNA

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
human
Sex:
male/female
Details on test animals and environmental conditions:
Two hundred fifty-five (49 males, 206 females) subjects were screened for the study. Two hundred forty-one (44 males, 197 females) subjects, ages 18 and older, signed the informed consent and were enrolled into the study.

Thirty-eight subjects, who were enrolled, failed to complete the study.

Two hundred three subjects (40 males, 163 females) completed all phases of the study.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: acetone
Concentration / amount:
1% v/v in acetone
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: acetone
Concentration / amount:
1% v/v in acetone
Details on study design:
Procedure from Protocol:
A series of paraspinal skin sites on the subject's back will be utilized for the Induction applications. Challenge patches will be applied to the opposite side of the back from the induction patches.
Test areas will be identified for each test article that will include the original (O) and move (M and M-1) sites. When multiple test articles are used, the assignment of test articles to individual skin sites will be rotated so that each test article occupies individual skin sites within the panel of test subjects, with approximately equal frequency, in order to elilninate any position bias.
The subjects enrolled for this study will be issued printed instructions and a test schedule.
Individual test articles will be applied to assigned sites on the skin for a contact period of approximately 24 hours per application. Test subjects will be instructed verbally to remove these patches the following day. Induction applications will be made three times per week for three successive weeks. The nine applications made during these three weeks will be termed Induction Application Nos. 1 through 9, respectively. The observation of the test sites and the subsequent applications are to be conducted at the test facility on Monday, Wednesday, and Friday during the same designated time frames. During the fourth week, any subject who was absent for one of the regularly scheduled induction applications will receive a make-up induction application.
All induction applications for an individual test article will be made to the same site (the site receiving the original test article at Induction Application No.1) unless reactions become so strong as to make this inadvisable. Assessment of an accumulated score of 2 or greater is considered to be a strong reaction (See 11.0 EVALUATIONS). In this case, subsequent applications of the offending test article will be made to an adjacent area, and a second change of site will be made if a second strong reaction occurs. If a third strong reaction to the test article is manifested, patches of this test article will be discontinued until after the rest period has been completed. Subjects experiencing unexpectedly strong reactions may also be excused from further induction patches by the Investigator. The use of a first and second adjacent site will be identified on the source document as M and M-1 sites, respectively, to indicate movement of test site from the original (O) application site.
A 10 to 17-day rest period will follow the final induction application. Following the rest period a challenge application of the test article(s) will be made to each subject. During the challenge application, the test article(s) will remain in contact with the skin for a period of approximately 24 hours. Test subjects will be instructed verbally to remove these patches the following day. Challenge will consist of application to a naive site (A) located away from the original (O) application site (e.g., opposite side of the back). Observations of the challenge sites will be conducted during the designated time frame on the second and fourth days post application.
Observations at the naive site during challenge and the patterns of reactivity during the induction period will provide a basis for an interpretation of contact sensitization.
Challenge controls:
Challenge controls not used in human studies, reaction evaluated by comparison to naive skin.
Positive control substance(s):
not specified
Remarks:
positive controls not used in human studies, reaction evaluated by comparison to naive skin.

Results and discussion

Positive control results:
Positive controls not used in human studies, reaction evaluated by comparison to naive skin.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
1.0% TXIB
No. with + reactions:
2
Total no. in group:
203
Clinical observations:
2 subjects out of 203 exhibited "slight, confluent or patchy erythema"
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1.0% TXIB. No with. + reactions: 2.0. Total no. in groups: 203.0. Clinical observations: 2 subjects out of 203 exhibited "slight, confluent or patchy erythema".
Reading:
2nd reading
Hours after challenge:
96
Group:
test group
Dose level:
1.0% TXIB
No. with + reactions:
2
Total no. in group:
203
Clinical observations:
2 subjects out of 203 exhibited "slight, confluent or patchy erythema"
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 96.0. Group: test group. Dose level: 1.0% TXIB. No with. + reactions: 2.0. Total no. in groups: 203.0. Clinical observations: 2 subjects out of 203 exhibited "slight, confluent or patchy erythema".
Reading:
other:
Hours after challenge:
0
Group:
negative control
No. with + reactions:
0
Total no. in group:
0
Remarks on result:
not measured/tested
Reading:
other:
Hours after challenge:
0
Group:
positive control
No. with + reactions:
0
Total no. in group:
0
Remarks on result:
not measured/tested

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the conditions of the study, HTR Code B (EAN 002800, PM 01315 "TXIB" Plasticizer) was found to be non-irritating and did not
elicit evidence of sensitization.
Executive summary:

A summary of the induction and challenge reactions, for the 203 subjects completing the study, and the overall conclusion of the irritation and sensitization potential of each test article is presented below:

Subject No. 147 experienced spreading of reaction beyond the patch area with all test articles which developed into a papular rash of the entire torso. The subject described a history of such reactions. The subject was discontinued from the study and followed to resolution on May 18,2001.

Subject No.102 exhibited slight reactions at challenge with every test article which were generally consistent with irritation.

HTR Code B (EAN 002800, PM 01315 "TXIB" Plasticizer): Responses during induction consisted of isolated instances of slight erythema and 2 occurrences of mild erythema. Responses during challenge consisted of 2 instances of slight erythema at 48 hours, one of which resolved by 96 hours and one of which did not (Subject No. 102). There was a single instance of slight erythema first appearing at the 96-hour evaluation (Subject No. 93). Under the conditions of the study, EAN 002800, PM 01315 "TXIB" Plasticizer was found to be non-irritating and did not elicit evidence of sensitization.