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Toxicological information

Skin sensitisation

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Administrative data

skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
nov-dec 2010
1 (reliable without restriction)

Data source

Reference Type:
study report

Materials and methods

Principles of method if other than guideline:
Repeated Insult Patch Test, protocol as defined by testing laboratory, no. BSUD01-OOl, based non international guidance and in compliance with Declarattion of Helsinki and GCP and monitored by an independent review board IRB. Guideline E6 for Good Clinical Practice, the
requirements of 21 CFR Parts 50 and 56, other applicable regulations, CPTC Standard Operating
Procedures, and the approved Study Protocol.
GLP compliance:
study was done under GCP
Type of study:
patch test
Justification for non-LLNA method:
A Patch test was deemed more reliabke than a LLNA test.

Test material

Details on test material:
PHOSFLEX 71B Sample T# 198 Lot: 10044H0100 Exp date:
Sept. 1, 2013

In vivo test system

Test animals

Details on test animals and environmental conditions:
Fifty-six (56) qualified_ subjects, male and female, ranging in age from 18 to
68 ·years, were selected for this evaluation. Fifty':three (53) subjects
completed this study. ·The remaining subjects discontinued their participation
for various reasons, none of which wcre related to the application of the test
material .

Inclusion Criteria:
Male and female subjects, age 168 and over.
b. Absence of any visible skin disease which might be confused with a skin
reaction from the test material.
c. Prohibition of use of topical or systemic steroids and/or antihistamines
for at least seven days prior to study initiation.
d. Completion of a Medical History form and the understanding and
signing of an Informed Consent form.
e. Considered reliable and capable of fo llowing direction

exclusion criteria:
111 health.
h. Under a doctor's care or taking medication(s) which could influence the
outcome of the study.
c. Females who are pregnant or nursing.
d. A history of adverse reactions to cosmetics or other personal care

Study design: in vivo (non-LLNA)

Inductionopen allclose all
epicutaneous, semiocclusive
other: isopropyl alcohol
Concentration / amount:
10% dilution
Challengeopen allclose all
epicutaneous, semiocclusive
other: isopropyl alcohol
Concentration / amount:
10% dilution
No. of animals per dose:
50 subjects . The first panel of 50 subjects will receive the 10% dilution. After 1 week of acceptable results, the
second panel of 50 subjects will have the 5% dilution. After another week of acceptable results, the final
group of 50 subjects will receive the 2.5% dilution.
Details on study design:
1. Semi- Occlusive Dressing
A semi-occlusive dressing consists of a 1" x 1" absorbent pad centered on a translucent,
perforated adhesive strip.
2 Patch Preparation
Approximately 0.2 ml of the test material solution will be applied to the absorbent pad
portion of the dressing. The test material solution on the patch will be allowed to volatilize
for more than 30 minutes prior to application to the back.

3. Induction Phase
Test material solution will be applied to the back between the scapulae and
beltline. The Induction patch will be applied to the same site 3 times a week
(e.g., Monday, Wednesday, and Friday), for 3 consecutive weeks for a total of 9
applications. Following supervised removal of the first Induction patch,
participants will be instructed to remove the patch at home, 24 hours following
each subsequent Induction patch application. Evaluation (Section 6.4) of the test
site will be made just prior to each re-application.
Should a subject be unable to report on an assigned test day, 1 makeup day will
be permitted. A second makeup day may be allowed only at the discretion of the
PI. All makeup days will be added to the Induction phase. If any subject does
not report as instructed, the subject will be discontinued from the trial.
Should a holiday, severe weather or other environmental condition occur during
the Induction phase, subjects who require a makeup day may experience a delay
between applications. The subject's evaluation score for the previous Induction
phase visit will be carried forward until the subject is evaluated again at the
Testing FaCility. Test sites will be marked with a surgical pen to ensure the continuity of repetitive
patch applications. Interim rest periods during the Induction phase consist of approximately 24 hours
following each Tuesday and Thursday patch removal, and 48 hours following each
Saturday patch removal.

4. Challenge Phase
Approximately 2 weeks following the final Induction patch applications, Challenge
patches will be applied to virgin test sites, adjacent to the original Induction patch
sites, following the same procedure described for Induction patch application.
The patches will be removed and the sites evaluated at the Testing Facility 24
hours post-application and evaluated again at the Testing Facility 72 hours postapplication.
Should a holiday, severe weather or other environmental condition occur during
the Challenge phase, the subject's evaluation score for the previous Challenge
phase visit will be carried forward until the subject is evaluated again at the
Testing Facility.

5. Re-Challenge Phase
In the event of a significant reaction occurring during the Challenge phase, the PI
may decide to schedule a Re-Challenge patch test for confirmatory purposes.
This follow-up investigation will be conducted approximately 2 weeks after the
completion of the Challenge phase. The application of the patch to a virgin site
on the back will be identical to the Challenge phase. Additionally, the subject will
conduct repetitive applications to the anti-cubital fossa for 4 consecutive days.
Observations of both test sites will be recorded 24 & 72 hours post application.

Challenge controls:
no controls
Positive control substance(s):
not required

Results and discussion

Positive control results:
no controls

In vivo (non-LLNA)

Key result
other: not relevant , see report attached
Dose level:
see report
No. with + reactions:
Total no. in group:
Remarks on result:
other: see report

Any other information on results incl. tables

Results tables added as PDF

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Migrated information Criteria used for interpretation of results: expert judgment
The results of each participant are appended (Table I).
Observations remained negative throughout the test interval.
Executive summary:

Under the conditions of this study, test material, PHOSFLEX 71 B Sample T#

198 Lot: I 0044HO I 00 Exp date: Sept. I, 20 13, did not indicate a potential for

dermal irritation or allergic contact sensitization.