Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15.11.-29.12.2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Test guideline
Qualifier:
no guideline available
GLP compliance:
no
Remarks:
according to GCP ICH guideline E6

Test material

Constituent 1
Chemical structure
Reference substance name:
Isopentyl salicylate
EC Number:
201-730-4
EC Name:
Isopentyl salicylate
Cas Number:
87-20-7
Molecular formula:
C12H16O3
IUPAC Name:
3-methylbutyl 2-hydroxybenzoate

Method

Type of population:
general
not specified
Ethical approval:
not specified
Subjects:
112 qualified subjects, male and female, ranging from 18 to 70 years
107 subjects completed the study, the reason for discontinuation were not related to the application of the test
Clinical history:
Inclusion criteria:
- 16 to 79 years (male and female)
- absence of any visible skin disease (confusion with skin reaction)
- prohibition of use of topical or systemic steroids and/or antihistamines for at least 7 d prior to study initiation
- completion of a Medical history Form and the understanding and signing of an informed Consent Form
- considered reliable and capable of following directions

Exclusion criteria:
- ill health under doctor's care or taking medication(s) which could influence the outcome of the study
- pregnant or nursing females
- a history of adverse reactions to cosmetics or other personal care products
Controls:
not specified
Route of administration:
dermal
Details on study design:
Methodology:
- test item concentration: 20% in DEP/EtOH 3:1
- approx. 0.2 ml of test material was applied to the upper back to a 1" x 1" absorbent pad portion of a clear, adhesive dressing which was applied to form a semi-occlusive patch

Induction phase:
- patches applied 3 times per week (Monday, Wednesday, Friday) for a total of 9 applications
- first scoring after 24 h after application
- evaluation before re-application
- rest periods of one day following each Tuesday and Thursday removal

Challenge phase:
- approx. 2 weeks after final induction patch application, a challenge patch was applied to a virgin test site adjacent to the original induction patch site following the same procedure as described for induction
- the patch was removed and the site scored at the clinic day 1 and day 3 post-application

Evaluation criteria (erythema and additional dermal sequelae):
0= no cicible skin reaction
0.5= barely perceptible
1= mild
2= moderate
3= marked
4= severe
E= edema
D= dryness
S= staining
P= papules
V= vesicles
B= bullae
U= ulceration
Sp= spreading

Erythema was scored numerically according to this key. If present, additional dermal sequelae were indicated by the appropriate letter code and a numerical value for severity.

Results and discussion

Results of examinations:
Observations remained negative throughout the test interval.
Few deviations from the study protocol were judged by the principal investigator as not affecting the test results, since observations remained negative.

Applicant's summary and conclusion

Conclusions:
Under the condtions of the study, the test material indicated no potential for dermal irritation or allergic sensitization.
Executive summary:

A Human Repeat Insult Patch Test (HRIPT) to determine by repetitive epidermal contact the potential of a test material to induce primary or cumulative irritation and/or allergic contact sensitization was performed. The study followed a generally accepted scientific test protocol and is described in sufficient detail. The test was performed accordng to GCP standard ICH E6.

112 qualified subjects, male and female, ranging from 18 to 70 years started and 107 subjects completed the study, the reason for discontinuation were not related to the application of the test.

Approximately 0.2 ml of test material at a concentration of 20% in DEP/EtOH 3:1was applied to the upper back to a 1" x 1" absorbent pad portion of a clear, adhesive dressing which was applied to form a semi-occlusive patch.

Patches were applied 3 times per week (Monday, Wednesday, Friday) for a total of 9 applications. The first scoring was 24 h after application and evaluation was before re-application. Rest periods of one day following each Tuesday and Thursday removal.

Approximately 2 weeks after final induction patch application, a challenge patch was applied to a virgin test site adjacent to the original induction patch site following the same procedure as described for induction. The patch was removed and the site scored at the clinic day 1 and day 3 post-application Erythema was scored numerically according to the key. If present, additional dermal sequelae were indicated by a appropriate letter code and a numerical value for severity.

Adverse events: subject #22 reported for a final post challenge observation. Diffuse erythema on the right side of her back (area about 4" x 6") and few small papules were also present but not associated with any patched test site, occurred two days after removal of the last patch. It was judged as unlikely to be related to the test material. Observations remained negative throughout the test interval.

Under the condtions of the study, the test material indicated no potential for dermal irritation or allergic sensitization.