Methyl phenylacetate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given, acceptable, well documented publication, no guideline and no GLP study.

Data source

Reference

Reference Type:

publication

Title:

The Freund's Complete Adjuvant Test and the Open Epicutaneous Test

Author:

Klecak, G.

Year:

1985

Bibliographic source:

Current Problems in Dermatology

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The open epicutaneous test represents an animal bioassay conducted with guinea pigs and designated to generate quantitative data. The generation of skin sensitization data includes a 3 step way. In the pretesting phase the primary irritating treshold concentration of the test substance is determined. The induction phase consists of a 3-week period of daily open applications. The final determination wheter sensitization has occured or not takes place in the final challenge phase.

GLP compliance:

not specified

Type of study:

open epicutaneous test

Justification for non-LLNA method:

A reliable test method (open epicutaneous test) was already performed to fulfill the data requirements of this endpoint.

Test material

Test material information

Constituent 1

Reference substance name:

Methyl phenylacetate

EC Number:

202-940-9

EC Name:

Methyl phenylacetate

Cas Number:

101-41-7

Molecular formula:

C9H10O2

IUPAC Name:

methyl phenylacetate

In vivo test system

Test animals

Species:

guinea pig

Strain:

not specified

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 300-450 g

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, open

Vehicle:

other: not specified

Induction 2

Concentration / amount:

3 phases:
Irritation: 0.025 mL of each test concentration
Induction: 21 x 0.1 mL (100 %, 30 %, 10 %, 3 %, 1 % and 0.3 %)
Challenge: 0.025 mL of minimal irritating concentration, max. non irritating concentration, lower primary non irritating concentrations

Challenge

Challenge 1

Route:

epicutaneous, open

Vehicle:

other: not specified

Challenge 2

Concentration / amount:

3 phases:
Irritation: 0.025 mL of each test concentration
Induction: 21 x 0.1 mL (100 %, 30 %, 10 %, 3 %, 1 % and 0.3 %)
Challenge: 0.025 mL of minimal irritating concentration, max. non irritating concentration, lower primary non irritating concentrations

No. of animals per dose:

5-7 groups of 6-8 males and females
20 animals at maximum are used, for controls 10 are used

Details on study design:

RANGE FINDING TESTS: 1 day before starting the induction procedure, the threshold irritating concentration of the test material is estimated on the guinea pigs subsequently used for the experimental group. A single application of 0.025 mL of each test concentration (e.g. 100, 30,10 and 3%) is simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. The minimal irritating and the maximal nonirritating concentrations are determined by an all-or-none criterion. The minimal irritating concentralion is defined as the lowest one causing skin irritation. The maximal nonirritating concentration is defined as the highest one not causing macroscopic skin reactions in any of the animals.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 21 applications
- Exposure period: For 3 weeks
- Test groups: 5-7 groups of 6-8 animals
- Site: on an area of 8 cm2 on the clipped flank skin
- Frequency of applications: daily
- Duration: 3 weeks
- Concentrations: if possible 100, 30, 10, 3, 1 and 0.3 %

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 21 and 35
- Test groups: Both the test and the control group
- Site: on the contralateral flank
- Concentration: 0.025 mL of minimal irritating concentration, max. non irritating concentration, lower primary non irritating concentrations (no data)
- Evaluation (hr after challenge): 24, 48 and 72 h

Challenge controls:

no data

Positive control substance(s):

no

Results and discussion

Positive control results:

no data

In vivo (non-LLNA)

Results

Key result

Reading:

other: Number of readings is not specified in the study

Group:

test chemical

Dose level:

0.025 mL of minimal irritating concentration, max. non irritating concentration, lower primary non irritating concentrations

No. with + reactions:

0

Remarks on result:

other: see Remark

Remarks:

Reading: other: Number of readings is not specified in the study. Group: test group. Dose level: 0.025 mL of minimal irritating concentration, max. non irritating concentration, lower primary non irritating concentrations . No with. + reactions: 0.0.

Any other information on results incl. tables

The test substance was found to have no sensitizing effect on the skin.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In the Open Epicutaneous Test the test substance did not induce skin reactions indicating a sensitising potential.

Executive summary:

To assess the potential of several substances including the test substance to cause skin irritation and to compare these results with human test results, an open epicutaneous test was performed on male and female guinea pigs. Therefore, after a range finding test to identify the minimal irritating and the maximal nonirritating concentrations, 0.1 mL of the test material (undiluted and diluted) was applied to the clipped flanks to groups of 6 animals per concentraton for induction. During induction, the test substance was applied daily for 20 days. The minimal irritating concentration was applied two times in the challenge phase (day 21 and 35). The skin reations were read after 24, 48 and/or 72 hours. On the basis of these resulst, the test substance was considered to be non sensitising. This result is supported by results of skin sensitization tests on humans, as described in this publication.