tetrakis(2,6-dimethylphenyl)-m-phenylene biphosphate

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05/26/2017 to 07/07/2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: KLIGMAN, A.M. & WOODING, W.M.

Version / remarks:

KLIGMAN, A.M. & WOODING, W.M. A method for the measurement and evaluation of irritants of human skin. J. Invest.. Derm. 49: 78-94, 1967.

Deviations:

not specified

GLP compliance:

not specified

Test material

Test material information

Test material form:

not specified

Details on test material:

Product Name: PX-200
Product Identification:Ref. 7711
Product Code: 063594-01

Specific details on test material used for the study:

No further details specified in the study report.

Method

Type of population:

general

Ethical approval:

confirmed and informed consent free of coercion received

Subjects:

Population Description
A total of 92 study subjects were recruited for this study. Out of those, 22 subjects (003, 004, 006, 008, 009, 011, 016, 021, 030, 031, 033, 037, 041, 048, 051, 054, 056, 059, 061, 076, 078 and 083) did not meet the inclusion criteria or presented any of the exclusion criteria.
The study was initiated with 70 subjects, being 63 female and 07 male subjects, aged from 18 to 67 years

Clinical history:

Inclusion Criteria
-Healthy study subjects;
-Intact skin on test site;
-Agreement to adhere to the procedures and requirements of the study and to report to the institute on the day(s) and at the time(s) scheduled for the assessments;
-Ability of giving a written consent for participating in the study;
-Aged from 18 to 70 years old;
-Study subjects of any gender;
-Phototype (Fitzpatrick): I to IV.

Non Inclusion Criteria
-Any skin marks on the test site that might interfere with the assessment of possible skin reactions (pigmentation disorders, vascular malformations, scars, increased pilosity, and great amounts of ephelides and nevus, sunburns);
-Active dermatosis (local or disseminated) that might interfere with the results of the study;
-Pregnancy or breastfeeding;
-Previous history of allergic reactions, irritation or intense feelings of discomfort to topical-use products, cosmetics or medication;
-Subjects with history of allergy to the material used in the study;
-Previous history of atopy;
-History of pathologies aggravated or triggered by ultraviolet radiation;
-Subjects suffering from immunodeficiencies;
-Intense exposure to sunlight or to sun tanning sessions up to 15 days before the initial evaluation;
-Intention of being intensely exposed to sunlight or to sun tanning sessions during the study period;
-Intention of sea bathing, going to the pool or sauna during the study;
-Subjects who practice water sports;
-Dermographism;
-Use of the following topical or systemic medications: immunosuppressive drugs, antihistamines, non-hormonal anti-inflammatory drugs, and corticosteroids within two weeks before the selection process;
-Oral or topical treatment with vitamin A acid and/or its derivatives up to 1 month before the study start;
-Aesthetic and/or dermatological treatment performed on the body within 03 weeks before selection;
-Intention of being vaccinated during the study period or up to 3 weeks before the study;
-Any conditions which the investigator finds compromising to the evaluation of the study;
-History of lack of adherence or unwillingness to adhere to the study protocol;
-Professionals who are directly involved in the performance of the current protocol as well as their relatives.

Route of administration:

dermal

Details on study design:

Study Design
Clinical, controlled and single-blind study.

Materials and Equipment
-Adhesive hypoallergenic card for patch testing with duly identified 1.0-cm2 filter paper discs;
-Semi-occlusive hypoallergenic tape;
-0.9% sterile physiological solution (NaCl 0.9%);
-Gloves, masks and caps;
-Surgical marker;
-Cotton swab;
-Scale
-Micropipette;
-Heating plate;
-Beaker;
-Dropper bottle;
-Transparent bottle.

Test Site
The product was applied to the study subjects back (scapular area).

Population Size
This study was conducted with 70 approved subjects so it could be completed with at least 50 responses.

Procedures
At first the study subjects were assessed by a dermatologist in order to verify the inclusion and exclusion criteria.
The patch test methodology (KLIGMAN & WOODING, 1967), also known as contact test or epicutaneous test, was used.
The product (0.05g/cm²) was distributed on the duly identified patch test filter paper disc and the 0.9% sterile physiological solution, used as control, was distributed on another duly identified disc.
The patch test containing both the test-product and control was then attached to the scapular area of the right or left back of the subjects.
Induction Period: the applications were performed three times a week, for three consecutive weeks, remaining in contact with the skin for 48 hours during the week and for 72 hours during weekends.
Rest Period: There was a rest period of at least 10 days following the induction period, when no patches were applied.
Challenge period: After the rest period, a patch with the test product and control was applied to the right or left back of the subjects on a virgin area, that is, where no patches had been applied before.
The patch was removed by the investigators after approximately 48 hours of contact with the skin.
The assessments (readings) were performed approximately 30 minutes (48h reading) and 24 hours (72h reading) after patch test removal.
The subjects were assessed at the end of the study by a dermatologist and supervised all along the study.

Assessment of Clinical Signs (Readings)
In case any subject presented any clinical sign during the readings, the assessment scale published by the International Contact Dermatitis Research Group - ICDRG (FISHER, 1995) would be used.

Results and discussion

Results of examinations:

Adherence to the Study
A total of 58 subjects completed the study.
A total of 09 subjects withdrew from the study due to personal reasons unrelated to the test product (025, 026, 045, 057, 079, 086, 087, 089 and 090).
Subjects 007, 013 and 014 presented irritation resulting from the exposure of the semi-occlusive tape (sticking plaster), probably due to individual pre-disposition, and for that reason the applications were discontinued and their data were not used in the study.

Dermatological Clinical Assessment
During the study, no subjects presented any clinical signs in the test product application site.
No subjects presented clinical signs in the control site.

Any other information on results incl. tables

Patch test assessments: Test-product

Subject No	Application	Reading + Application	Reading + Application	Reading + Application	Reading + Application	Reading + Application	Reading + Application	Reading + Application	Reading + Application	Reading	Application	Reading	Reading
001	0	0	0	0	0	0	0	0	0	0	0	0	0
002	0	0	0	0	0	0	0	0	0	0	0	0	0
005	0	0	0	0	0	0	0	0	0	0	0	0	0
007	0	0	0	0	0	0	0	R	R	R	R	R	R
010	0	0	0	0	0	0	0	0	0	0	0	0	0
012	0	0	0	0	0	0	0	0	0	0	0	0	0
013	0	0	0	0	0	0	R	R	R	R	R	R	R
014	0	0	0	0	0	0	R	R	R	R	R	R	R
015	0	0	0	0	0	0	0	0	0	0	0	0	0
017	0	0	0	0	0	0	0	0	0	0	0	0	0
018	0	0	0	0	0	0	0	0	0	0	0	0	0
019	0	0	0	0	0	0	0	0	0	0	0	0	0
020	0	0	0	0	0	0	0	F	0	0	0	0	0
022	0	0	0	0	0	0	0	0	0	0	0	0	0
023	0	0	0	0	0	0	0	0	0	0	0	0	0
024	0	0	0	0	0	0	0	0	0	0	0	0	0
025	F/R	R	R	R	R	R	R	R	R	R	R	R	R
026	0	0	0	F	0	0	F/R	R	R	R	R	R	R
027	0	0	0	0	0	0	0	0	F	0	0	0	0
028	0	0	0	0	0	0	0	0	0	0	0	0	0
029	0	0	0	0	0	F	0	0	0	0	0	0	0
032	0	0	0	0	0	0	0	0	0	F	0	0	0
034	0	0	0	0	0	0	0	0	0	0	0	0	0
035	0	0	0	0	0	0	0	0	0	0	0	0	0
036	0	0	0	0	0	0	0	0	0	0	0	0	0
038	0	0	0	0	0	0	0	0	0	0	0	0	0
039	0	0	0	0	0	0	0	0	0	0	0	0	0
040	0	0	0	0	0	0	0	0	0	0	0	0	0
042	0	0	0	0	F	0	0	0	0	0	0	0	0
043	0	0	0	0	0	0	0	0	0	0	0	0	0
044	0	0	0	0	0	0	0	0	F	0	0	0	0
045	F/R	R	R	R	R	R	R	R	R	R	R	R	R
046	0	0	0	0	0	0	0	0	0	0	0	0	0
047	0	0	0	0	0	0	0	0	0	0	0	0	0
049	0	0	0	0	0	0	0	0	0	0	0	0	0
050	0	0	0	0	0	0	0	0	0	0	0	0	0
052	0	0	0	0	0	0	0	0	0	0	0	0	0
053	0	0	0	0	0	0	0	0	0	0	0	0	0
055	0	0	0	0	0	0	0	0	0	0	0	0	0
057	0	0	F/R	R	R	R	R	R	R	R	R	R	R
058	0	0	0	0	0	0	0	0	0	0	0	0	0
060	0	0	0	F	0	0	0	0	0	0	0	0	0
062	0	0	0	0	0	0	0	0	0	0	0	0	0
063	0	0	0	0	0	0	0	0	F	0	0	0	0
064	0	0	0	0	0	0	F	0	0	0	0	0	0
065	0	0	0	0	0	0	0	0	F	0	0	0	0
066	0	0	0	0	0	0	0	0	0	0	0	0	0
067	0	0	0	0	0	0	0	0	0	0	0	0	0
068	0	0	0	0	0	0	0	F	0	0	0	0	0
069	0	0	0	0	0	0	0	0	F	0	0	0	0
070	0	0	0	0	0	0	0	0	0	0	0	0	0
071	0	0	0	0	0	0	0	0	0	0	0	0	0
072	0	0	0	0	0	0	0	0	0	0	0	0	0
073	0	0	0	0	0	F	0	0	0	0	0	0	0
074	0	0	0	0	0	0	0	0	0	0	0	0	0
075	0	0	0	0	0	0	0	0	0	0	0	0	0
077	0	0	0	0	0	0	0	0	0	0	0	0	0
079	0	0	0	F	F/R	R	R	R	R	R	R	R	R
080	0	0	0	0	0	0	0	0	0	0	0	0	0
081	0	0	0	0	0	0	0	0	0	0	0	0	0
082	0	0	0	0	0	0	0	0	0	0	0	0	0
084	0	0	0	0	0	0	0	0	0	0	0	0	0
085	0	0	0	0	0	0	0	0	0	0	0	0	0
086	0	0	0	F	0	0	0	0	F/R	R	R	R	R
087	F/R	R	R	R	R	R	R	R	R	R	R	R	R
088	0	0	0	0	0	0	0	0	0	0	0	0	0
089	F/R	R	R	R	R	R	R	R	R	R	R	R	R
090	F/R	R	R	R	R	R	R	R	R	R	R	R	R
091	0	0	0	0	0	0	0	0	F	0	0	0	0
092	0	0	0	0	0	0	0	0	0	0	0	0	0

Caption:

X = Not Applied / Reading Not Performed                   0 = No reaction

F = Absence                                                    1 = Mild Erythema

R = Removed from the Study                                 2 = Clear Erythema

DK = Darkening                                                 3 = Erythema + Edema + Papules

DY = Dryness                                                   4 = Erythema + Edema + Papules + Vesicles

F/R = Absence / Removed from the Study

Applicant's summary and conclusion

Conclusions:

According to the methodology used to assess the skin sensitization potential of the product PX-200, submitted by the company DAIHACHI CHEMICAL INDUSTRY CO.,LTD. it could be concluded that:
-During the study, no subjects presented skin clinical signs related to the product.
-The product did not induce a skin sensitization process in the study group.
-The product was considered safe under the study conditions.

Executive summary:

STUDY OBJECTIVE

To prove the absence of the skin sensitization potential of a product applied to the skin, under maximized conditions, with controlled product amount and application site, supervised by a dermatologist.

 

METHODOLOGY

Both the test-product and control were applied to patch test filter paper discs and then applied to the right or left back (scapular area) of the study subjects. The applications were performed on Mondays, Wednesdays and Fridays, during 3 consecutive weeks. Forty-eight hours (48h) after the application, the patch test was removed by trained technicians and, approximately 30 minutes after the patch test removal, the site was assessed in order to check the presence of possible clinical signs.

After this period (induction) there was a, minimum, 10 day-period when no patch was applied to the study subjects' back (rest period).

Then, the challenge period started. A single application of the patch test was performed, followed by readings after 48h and 72h.

The study subjects were assessed by a dermatologist at the start and at the end of the study and supervised all along the study.

 

STUDY LENGTH

6 weeks.

 

FREQUENCY OF APPLICATION

9 applications on the 3 first weeks (induction period).

1 application on the last week (challenge period).

 

APPLICATION SITE

Back (Scapular area).

 

NUMBER OF SUBJECTS

58 study subjects.

 

POPULATION DESCRIPTION

Female and male, age range from 18 to 67 years old, phototype II to IV (Fitzpatrick).

 

ETHICS

This study was conducted in conformance with the Declaration of Helsinque principles, the applicable regulatory requirements, including Resolution CNS no. 466/12, and in spirit of the Good Clinical Practices (Document of the Americas and ICH E6: Good Clinical Practice).

 

RESULTS

During the study, no subjects presented skin clinical signs related to the product.

 

CONCLUSION

The product did not induce a skin sensitization process in the study group.

The product was considered safe under the study conditions.