Ethyl 3-(2,4-dimethyl-1,3-dioxolan-2-yl)propanoate

Sensitisation data (human)

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:

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:

2010

Report date:

2010

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A modified version of repeated insult patch test (HRIPT) was performed on 109 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. After 2 wks of induction the treatment sites were challenged with two concurrent sets of patches at the original induction treatment sites and one set at naive site. The reactions were scored 24 hrs after each patch application (i.e. on wednesdays and fridays) and 48 hrs (i.e. on mondays after patches had been removed) in the induction phase and at 24rs and 48 hrs after patch application in the challenge phase.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

ethyl 3-(2,4-dimethyl-1,3-dioxolan-2-yl)propanoate

EC Number:

700-636-5

Cas Number:

5413-49-0

Molecular formula:

C10H1804

IUPAC Name:

ethyl 3-(2,4-dimethyl-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: 109.
- Sex: 25 males and 84 females.
- Age: Females (18 to 68 yrs), males (20-70 yrs)

Controls:

No

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 Webril 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, treatment sites were scored for reactions at 24 hrs after each patch application (i.e. on wednesdays and fridays) and 48 hrs (i.e. on mondays after patches had been removed) for each of 9 exposures in the induction phase and at 24 and 48 hrs after patch application in the challenge phase. Scoring was done as defined as follows:
No evidence of irritation/adverse effect - 0
If adverse effects (i.e. gross skin changes) was seen then grading was done as follows:
Morphology Visible changes Grade
Subclinical stage None 0
Inflammation
Vascular dilation Faint redness with poorly defined margins 1
Redness with well-defined margins 2
Infiltration Redness plus well-defined edema 3
Redness plus papules, or vesicles ot ulceration 4
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:

SYMPTOMS
NO. OF PERSONS COMPLETED THE STUDY: The study was initiated on 109 panelists, however only 106 of the 109 subjects were in compliance with the number of required applications/examinations during the induction and the challenge study

- Frequency, level, duration of symptoms observed: No responses were observed after induction or challenge application of the product.

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: None
- Number of subjects with equivocal reactions: None
- Number of subjects with irritating reactions: None

Significance of the responses:
Initial induction phase: no response was noted in any of the 106 subjects who participated in this phase of the study. The product was devoid of any clinically significant skin sensitizing propensities.
Challenge phase- Original/ naive contact site: no response was noted in any of the 106 subjects who participated in this phase of the study. The product was devoid of any clinically significant skin sensitizing propensities.

Applicant's summary and conclusion

Conclusions:

The test substance did not produce skin sensitization in the human subjects in this repeated insult patch test (HRIPT).
It was neither a clinically signifacant skin irritant nor a sensitizer.

Executive summary:

A human repeated insult patch test (HRIPT) was performed to study the effect of repeated applications of the test substance on human skin.

A total of 109 subjects participated in the study. Subjects were exposed to nine induction patches for three weeks containing 200 µL of the test substance. Patches were removed 24 h after each application and patch sites were graded at 24 and 48 h after patch application prior to the next patch application.

After a two week rest period, subjects were challenged with the test substance (24 h patch exposure) with duplicate patch at the original site and a fresh site on the other arm. Challenge patch sites were graded at 24 and 48 h after patch application.

In this study, 106 subjects completed the study. Serial application of the test substance produced no irritation or clinically significant skin sensitizing properties.

Based on above results, it was concluded that the test substance did not produce skin sensitization in the human repeated insult patch test.