Reaction mass of 2-methoxy-6-methylocta-1,5-diene and 2-methoxy-6-methylocta-2,5-diene

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

8 October 2018 to 16 November 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Test guideline

Qualifier:

according to guideline

Guideline:

other: Shelanski Method

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of 2-methoxy-6-methylocta-1,5-diene and 2-methoxy-6-methylocta-2,5-diene

EC Number:

950-170-3

Molecular formula:

C10H18O

IUPAC Name:

Reaction mass of 2-methoxy-6-methylocta-1,5-diene and 2-methoxy-6-methylocta-2,5-diene

Specific details on test material used for the study:

PG-RAW-0004 at 2.5% in vehicle EtOH/diethyl phthalate (DEP) (1:3 w/w)

Method

Type of population:

general

Subjects:

A total of 112 male and female subjects, ranging in age from 21 to 70 years and in generally good health, were selected for the study. Subjects who met all of the inclusion criteria and none of the exclusion criteria listed in the study protocol were enrolled for participation.

INCLUSION CRITERIA
a. Subject is male or female between the ages of 18 and 70 years;
b. Female subjects who are sexually active are using adequate method of birth control;
c. Subject does not exhibit any skin diseases which might be confused with a skin reaction from the test material;
d. Subject is absent of any visible or known pre-existing skin disease which might be confused with a skin reaction from the test material, or which may be reasonably expected to affect the outcome of the study. This includes psoriasis or active eczema even if currently controlled through medication.
e.Subject agrees to avoid exposure of the test sites to the sun and to refrain from visits to tanning salons during the course of this study;
f. Subject agrees to refrain from getting patches wet and from scrubbing or washing the test area with soap or applying powder, lotions or personal care products to the area during the course of the study;
g. Subject has signed an Informed Consent in conformance with 21CFR Part 50: “Protection of Human Subjects;”
h. Subject has completed a HIPAA Authorization Form in conformance with 45CFR Parts 160 and 164;
i. Subject is in generally good health and has a current Subject Profile
j. Subject is dependable and able to follow directions as outlined in the protocol.

EXCLUSION CRITERIA
a. Subject is pregnant, nursing, or planning to become pregnant, or not using adequate birth control;
b. Subject is currently using any systemic or topical corticosteroids, anti-inflammatory drugs, or antihistamines on a regular basis;
c. Subject reports allergies to cosmetics, toiletries, or personal care products;
d. Subject exhibits any skin disorders, sunburn, scars, excessive tattoos, etc. in the test area;
e. Subject has scheduled, or is planning to undergo, any medical or surgical procedures during the 6-week course of the study.

Controls:

DI H2O at 2.5w/w% in EtOH/DEP (1:3 w/w)

Route of administration:

dermal

Details on study design:

The study consisted of an induction phase, a challenge phase, and, at the discretion of the Principal Investigator and at the approval of the Sponsor, a Re-Challenge Test. During the Induction Phase, the test materials were applied to the same location on the back of each subject three times per week for a total of nine applications, with 24-hour rest periods, except Fridays, in between applications, or as specified in Section 10.0. Test sites were examined for dermal irritation at each visit prior to reapplication of the test materials. Approximately 10 to 21 days after the Induction Phase, subjects returned to the laboratory for the Challenge Phase. The test materials were applied to virgin sites on the back under the appropriate patch type, and were removed by clinic staff approximately 24 hours later. Test sites were examined for signs of dermal irritation or sensitization. At the discretion of the Principal Investigator and with the Sponsor’s approval, a subject may have been required to return to the lab for a Re-Challenge Test if reactions indicative of sensitization were observed during the Challenge Phase. During the Re-Challenge Phase, the test material was applied to a virgin site on the upper arm or back under the same conditions of the Challenge Phase and the subject was examined for dermal reactions. At the Sponsor’s request, additional products (“omission products” or individual components) may have been tested and/or other conditions may have been used.
This study was conducted in a population of male and female subjects between the ages of 18 and 70 years in general good health who did not exhibit any skin diseases, disorders, or abnormalities. Subjects could not use any systemic or topical corticosteroid, anti-inflammatory drugs, or antihistamines, and could not have a history of allergies to cosmetics, toiletries, or personal care products. Subjects agreed to comply with all study requirements, which included not removing patches for 24 hours and avoiding sun exposure. Subjects could not be pregnant, nursing, or planning to become pregnant. Subjects completed a HIPAA Authorization Form in conformance with 45 CFR Parts 160 and 164 prior to participating in studies at the investigating laboratory, and an Informed Consent Form in conformance with 21CFR Part 50: “Protection of Human Subjects;” for each study.

Results and discussion

Results of examinations:

This study was initiated with 112 subjects. Six subjects discontinued study participation for reasons unrelated to the test material. A total of 106 subjects completed the study.
No adverse events were reported during the study.

Applicant's summary and conclusion

Conclusions:

Based on the test population of 106 subjects and under the conditions of this study, PG-RAW-0004 at 2.5 w/w% in vehicle EtOH/DEP (1:3 w/w) did not demonstrate a potential for eliciting dermal irritation or sensitization under the following test conditions: 0.15ml of the test material applied to a 3.63 cm2 occlusive patch, equivalent to approximately 1033 ug/cm2.

Executive summary:

One hundred and twelve subjects participated in evaluating the potential of PG-RAW-0004 (2.5wt% in EtOH/DEP (1:3 w/w)) to elicit dermal irritation and/or induce sensitization. DI H2O (2.5wt% in EtOH/DEP (1:3 w/w) was tested as a control.

The test material and control were applied under occlusive patch to the upper back of each subject and were allowed to remain in direct skin contact for a period of 24 hours. Patches were applied to the same site on Monday, Wednesday, and Friday for a total of 9 applications during the Induction Period. The sites were graded by a CRL technician for dermal irritation 24 hours after removal of the patches by the subjects on Tuesday and Thursday and 48 hours after removal of the patches on Saturday.

Approximately 10 to 21 days after the Induction Phase, challenge patches were applied to previously untreated test sites on the back. After 24 hours, the patches were removed by a CRL technician and the test sites were evaluated for dermal reactions. The test sites were re-evaluated at 48 and 72 hours after application. Subjects exhibiting reactions during the Challenge Phase of the study may have been asked to return for a 96-hour reading.

One hundred and six subjects completed the study. The test material and control did not demonstrate a potential for eliciting dermal irritation or sensitization under the following test conditions: 0.15ml of the test material applied to a 3.63 cm2 occlusive patch, equivalent to approximately 1033 ug/cm2.