Enzymatic hydrolysis products of Ophiopogon japonicus, Liliaceae, root

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation, other

Remarks:

Human Repeat Insult Patch Test

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2 November 2015 - 9 January 2016

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Human Repeat Insult Patch Test using generally-accepted methods.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Repeated Insult Patch Test was performed to confirm that repeated applications of the product under maximized conditions, in healthy subjetcs, does not induce delayed contact allergy reactions. A secondary objective is to determine the irritating potential of the product first after a single application and second after repeated applications.

GLP compliance:

no

Remarks:

study has been conducted in the spirit of the good Clinical Practice

Type of study:

patch test

Justification for non-LLNA method:

HRIPT study in human volunteers already available

Test material

Test material information

Constituent 1

Reference substance name:

Enzymatic hydrolysis products of Ophiopogon japonicus, Liliaceae, root

EC Number:

812-241-6

Cas Number:

952500-62-8

IUPAC Name:

Enzymatic hydrolysis products of Ophiopogon japonicus, Liliaceae, root

Test material form:

liquid

Details on test material:

transparent solution
pH 5.2

In vitro test system

Details on the study design:

Not applicable

In chemico test system

Details on the study design:

Not applicable

In vivo test system

Test animals

Species:

other: Human

Details on test animals and environmental conditions:

- Number of subjects empanelled: 110
- Number of subjects completed the study: 106 (4 drop out)
- Age: 18-68 years
- The subjects choosen cooperative subjects, aware of tge necessity and duration of the controls so that perfect adhesion to the procol established by Dermscan could be expected.
Inclusion citeria were: subjects having given their informed, written consent and subjects without scars, tatoos, any pigmentary marks, ecessive pilosity and uneven skkin tone or active dermal lesions, on the concerned areas of the back.

Study design: in vivo (non-LLNA)

Details on study design:

Monocentric and simple blind study.

TYPE OF TEST(S) USED: patch test

ADMINISTRATION
- Type of application: occlusive
- Application area: The back: homolateral (Induction site) and contralateral (challenge site)
- Description of patch: Finn's chamber occlusive (8 mm) (50 mm²)
- Volume applied: 25 µL
The studied product was applied to a cleansed (with physiological saline or water) and dry skin.
- Application frequency:
Induction phase: 3 times a week during 48 hours (72 h for the week-end)
Challenge phase: once durig 48 hours
- Study schedule: cf Any other information on materials and methods Table 2

EXAMINATIONS
After each application, the patch is removed and the clinical examination is performed by the investigator 30 minutes later in order to eliminate the pressure and the occlusive effects. The resulf ot the examination id negative if the skin looks normal. The clinical examination is made on the back using the following criteria and scale:

Clinical criteria regarding the irritating potential (induction phase)
- Grading/Scoring system:
0 = No erythema, no edema
0.5 = very slight = erythema: bareky perceptible: pinkish coloration of one part of the tested area and palpable and barely visible edema
1 =Slight = eruthema: pinkish coloration of the complete tested area or rather visible on one part of the tested area, and palpable and visible edema
2 =Net = obvious erythema covering the whole tested arean and obvious edema (thickness <1mm) with or without blister or vesible
3 = important = severe erythema covering all the tested area or obvious erythema diffusion outside the tested area, and severe edema (thickness > 1mm of diffusiong outside the tested area) with our without vesicle or blister.

Clinical criteria regarding the sensitizing potential ( challenge phase) : cf. Any other information on materials and methods Table 1

Results and discussion

In vivo (non-LLNA)

Results

Key result

Reading:

1st reading

Group:

test chemical

Dose level:

25 µL of OF14 ATS

No. with + reactions:

0

Total no. in group:

106

Clinical observations:

During the induction or challenge phase, no skin reactions were observed. “OF14 ATS” showed a score of 0.01. No reaction ++  nor +++  was observed, so the product “OF14 ATS” can be considered as non-sensitizing

Any other information on results incl. tables

RESULTS INTERPRETATION:

At the end of the 9 readings of the induction phase, the average score of each subject (Cumulative irritation index CII) is calculated by adding the scores obtained for each readings and by dividing this sum by the actual number of readings.

The irritating potential of the product is estimated by calculating the mean of the reactions observed during the induction phase in order to obain the Mean cumulative Irritation Inde (MCII). the obtained index allows to arbitrarily classify the studied product according to the following scale:

M.C.I.I.  Classe  M.C.I.I. < 0.25  Non irritating (NI)  0.25 ≤M.C.I.I. < 0.50  Very slightly irritating (VSI)  0.5≤ M.C.I.I. < 1  Slightly irritating (SI)  1 ≤M.C.I.I. < 2  Moderately irritating (MI)  M.C.I.I. ≥2  Irritating (I)

Challenge phase:

A possible reaction during the induction or challenge phase is assessed from 0 to 3 according to ICDRG (International Contact Dermatitis Research Group) (see table 1) . During the Challenge phase, the reading is done 30 minutes after patch-tests removal and 48 hours later. The sensitizing potential of the product is assessed by the readings on D37 and D39 according to the following criteria reaction++ or +++ in the absence of added irritation phenomenon. The presence of only one case of active sensitization or controlateral side leads to the conclusion "Potentially sensitizing product".

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under these study conditions, the product “OF14 ATS” can be considered non-irritating and non-sensitizing

Executive summary:

A panel of 110 male and female human volunteers participated in a repeat insult patch test in which a test product OF14 ATS applied to the back of the subjects under occlusive patches. 106 subjects completed the study.

During the induction or challenge phase, no skin reactions were observed.“OF14 ATS” showed a score of 0.01. It can thus be considered as non-irritating.

No reaction ++  nor +++  was observed, so the product “OF14 ATS” can be considered as non-sensitizing

Under these study conditions, the product “OF14 ATS” can be considered non-irritating and non-sensitizing