Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 6th to August 13th, 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Principles of method if other than guideline:
A modified version of repeated insult patch test (HRIPT) was performed on 107 subjects to study the effect of repeated application of the test substance to human skin. The study was conducted in two phases 1) Induction phase and 2) Challenge phase. In the induction phase, patches were applied in a row on the left side of the back of the subject and left in place 24 hrs at each of nine applications over a period of three weeks.
GLP compliance:
yes
Remarks:
Good clinical practice

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethyl 3-[4-(hydroxymethyl)-2-methyl-1,3-dioxolan-2-yl]propanoate
EC Number:
700-637-0
Cas Number:
902272-78-0
Molecular formula:
C10H18O5
IUPAC Name:
Ethyl 3-[4-(hydroxymethyl)-2-methyl-1,3-dioxolan-2-yl]propanoate

Method

Type of population:
general
Ethical approval:
other: Volunteers were given an informed consent document to read.
Subjects:
- Number of subjects exposed: 106-107.
- Sex: 25 males and 84 females.
- Age: Females (18 to 68 yrs), males (20-70 yrs)
Route of administration:
dermal
Details on study design:
TYPE OF TEST(S) USED: Human repeated insult patch test (HRIPT).

ADMINISTRATION
- Type of application: partially occlusive.
- Description of patch: the test patch consisted of a 2 cm X 2 cm absorbent pad centered on the adhesive-coated surface of a 2 cm X 4 cm plastic film.

Procedure:
1) Skin at the contact site was marked to facilitate examination after removal of the applied device.
2) The webril pad of the patching device was infused with 200 µl of the test material.
3) The study was conducted in following two phases:
Induction phase: patches were applied on the same site on the left side of the back of the subject at each nine applications for three weeks unless severity of a reaction made the application inadvisable.
Challenge phase: after 2 wks of the induction, treatment sites were challenged with two concurrent sets of patches at the original induction treatment sites and one set at naive site.
Make up session: a make up session was arranged after the last induction application for the panelists with earlier absence.
4) The patches were positioned on the designated site and firm pressure was applied to make a close skin contact.
5) The patch was peeled off as gently as possible from the skin 24 hrs after application of each of the nine induction patches and the challenge patches.
6) In induction phase, the skin of the contact sites was graded and the grades recorded on Wednesdays, Fridays (i.e., 24 h after patch removal) and Mondays (i.e., 24 h after patch removal). During the challenge phase, the skin of the contact sites was graded within moments after the patches had been removed (24 h post application) and again 24 h later. Follow-up examinations were conducted thereafter only if adverse effects were present.
7) A follow up phase on weeks 7 and 8 was conducted. Subjects were given opportunity to give any information concerning effects which could be helpfull for characterization of the product and communicate the need for the treatment of newly occuring responses if any.

Results and discussion

Results of examinations:
Induction phase
No responses were noted on any of the 107 subjects who underwent at least one post-application examination. The absence of responses characterizes the test substance as one which is devoid of clinically significant skin-irritating properties.

Challenge phase
- Original Contact Sites: no responses were noted on any or the 106 subjects who participated in this phase of the study. The absence of responses characterizes the product as one which is devoid of clinically significant skin sensitizing properties.
- Naive Contact Sites: no responses were noted on any of the 106 subjects who participated in this phase of the study. The absence of responses characterizes test substance as one which is devoid of clinically significant skin sensitizing properties.

Applicant's summary and conclusion

Conclusions:
The test substance is considered to be neither a skin irritant nor a skin sensitiser in a modified HRPIT test.
Executive summary:

A modified human repeated insult patch test (HRIPT) was performed under double-blind conditions to evaluate the effects of repeated application of test substance to human skin. A total of 106-107 male and females were employed in the study. Subjects were exposed to 9 induction patches containing test solution under semi-occlusive on a Monday, Wednesday and Friday regimen for 3 subsequent wks. The patches were applied at left side of the back of each subject for 24h and then removed. After a 14 d rest period subjects were challenged with two set of patches, one at original site and other at naive site. The application site was observed for 24 and 48 h after challenge. The symptoms observed were evaluated according to scoring system.

The test substance did not produce any skin irritation or sensitization in humans after induction or challenge application.

Under the test conditions, the test substance is considered to be neither a skin irritant nor a skin sensitiser.