Registration Dossier

Administrative data

Description of key information

According to clinical study (human repeat patch test) test item was considered as non-irritating and non-sensitising.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
Human Repeat Insult Patch Test
Type of information:
experimental study
Adequacy of study:
key study
Study period:
4 January to 16 March 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Reason / purpose:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
MARZULLI-MAIBACH METHOD: The Marzulli-Maibach test is a reference test to study the sensitizing potential of a product. The investigational product was applied under maximized conditions (occlusion) during 3 weeks (Induction phase). After a two-week resting period, the investigational product was re-applied on the same site (Challenge phase). If the investigational product was allergenic, it induced a cutaneous reaction during the challenge phase.
GLP compliance:
no
Remarks:
Good clinical practice
Type of study:
other: Study with volunteers
Justification for non-LLNA method:
Available study on volunteers
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Robertet / 1968538
- Appearance: Orange-Brown Solid

Species:
other: Human
Strain:
other: Not relevant
Sex:
male/female
Details on test animals and environmental conditions:
- Number of subjects recruited: 115
- Number of subjects exposed: 102
- Sex: 26 men and 76 women
Positive control results:
No positive control
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
FENUGREEK ABS 220275 1% (456 µg/cm2) EtOH/DEP(25/75) lot 1968538
No. with + reactions:
0
Total no. in group:
102
Clinical observations:
No significant clinical manifestation of intolerance or allergy was observed by the investigator.
Remarks on result:
no indication of skin sensitisation
Reading:
other: Non performed
Group:
negative control
Remarks on result:
not measured/tested
Reading:
other: Non performed
Group:
positive control
Remarks on result:
not measured/tested

Table 7.10.4/1: Induction phase – results

Days

Investigational product

% of subjects - reaction

Semi-Occlusive control

% of subjects - reaction

Day 1

Normal examination

0

Normal examination

0

Day 3

No reaction

0

No reaction

0

Day 5/6*

No reaction

0

No reaction

0

Day 8

No reaction

0

No reaction

0

Day 10

No reaction

0

No reaction

0

Day 12/13*

No reaction

0

No reaction

0

Day 15

No reaction

0

No reaction

0

Day 17

No reaction

0

No reaction

0

Day 19/20*

No reaction

0

No reaction

0

Day 22

No reaction

0

No reaction

0

Day 24**

No reaction

0

No reaction

0

* Subjects no. 104, 105, 106, 107 and 108 began the study 2 days later, so they did not have any visit at Day 5, Day 12 and Day 19, but at Day 6, Day 13 and Day 20.

** Additional application day for subjects no. 3, 13, 67, 69, 89, 95, 97 and 103 as they did not have any application nor reading performed one day during the induction phase.

Table 7.10.4/2: Challenge phase – results

Days

Sites

Investigational product

% of subjects - reaction

Semi-Occlusive control

% of subjects - reaction

Day 34/36*

H

Normal examination

0

Normal examination

0

C

Normal examination

0

Normal examination

0

Day 36/38*

H

No reaction

0

No reaction

0

C

No reaction

0

No reaction

0

Day 37/39*

H

No reaction

0

No reaction

0

C

No reaction

0

No reaction

0

Day 38/40*

H

No reaction

0

No reaction

0

C

No reaction

0

No reaction

0

H: homolateral site;C: contralateral site

* Subjects no.104, 105, 106, 107 and 108 began the study2days later, therefore their challenge phase was performed on Day34,Day 36,Day37and Day38instead of Day36,Day38,Day39and Day 40.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the study, the investigational product FENUGREEK ABS 220275 1% (456 µg/cm2) EtOH/DEP(25/75) tested undiluted, under semi occlusive patch, can be considered as non-sensitizing.
Executive summary:

A cutaneous tolerance and sensitizing potential study of the investigational product, FENUGREEK ABS 220275 1% (456 µg/cm2) EtOH/DEP(25/75) tested undiluted was conducted by patches application, according to the Marzulli-Maibach sensitization method. The data of 102 female and male subjects aged from 19 to 63 years old were analyzed during the study. The subjects were willing and able to give a written informed consent. The study was carried out at the clinical unit of Skopje in MACEDONIA. The study was blinded and randomized.

Duration:Induction phase: 3 weeks (3 times a week during 48 hours or 72 hours); Duration Resting phase: 14 days; Challenge phase: 1 week (once during 48 hours)

 

INDUCTION PHASE: During the Induction Phase, the investigational product was applied (160 µL) on a predetermined site under semi occlusive patch (back). A semi-occlusive patch receiving no product was applied in the same conditions and was considered as a non-treated control. Each time, the patches (treated and non-treated) remained applied during 48 or 72 hours before removal and replaced on the same site.

RESTING PHASE: During the 14-day Resting Phase, no product was applied on the sites used during the Induction phase or on the contralateral split-back which was used during the Challenge phase.

CHALLENGE PHASE: During the challenge phase (Day 34/36*), the investigational product was applied under semi occlusive patch on the induction sites and on the contralateral sites. A semi occlusive patch receiving no product was applied in the same conditions and was considered as a non-treated control. The patches (treated and non-treated) remained applied during 48 hours and removed afterwards.

 

A clinical examination was performed by the investigating dermatologist during the Induction Phase on Days 1, 3, 5/6, 8, 10,12/13,15, 17,19/20 and 22/24,and during the Challenge Phase on Days 34/36, 36/38, 37/39 and 38/40.

 

During the induction phase, no sign was observed on the control site and the investigational product site. During the challenge phase, no sign was observed on the control site and on the investigational product site, neither on the homolateral side nor on the controlateral site. In this study, no adverse event or serious adverse event was observed by the investigating dermatologists. No significant clinical manifestation of intolerance or allergy was observed by the investigator. The investigational product presents an irritation index of: Z = 0.000; the investigational product is therefore considered as practically non-irritant.

 

Under the conditions of the study, the investigational product FENUGREEK ABS 220275 1% (456 µg/cm2) EtOH/DEP(25/75) tested undiluted, under semi occlusive patch, can be considered as non-sensitizing.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Under the conditions of the study, the investigational product FENUGREEK ABS 220275 1% (456 µg/cm2) EtOH/DEP(25/75) tested undiluted, under semi occlusive patch, can be considered as non-sensitizing.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In a human repeat insult patch test, the test item was concluded to be non-irritating and non-sensitising.

Based on this result and due to the nature of the main constituents of the registered substance, the registered substance does not need to be classified as skin sensitiser.