Phenylacetic acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journals

Data source

Reference

Reference Type:

publication

Title:

The Freund's Complete Adjuvant Test and the Open Epicutaneous Test for the given test chemical.

Author:

G. Klecak

Year:

1985

Bibliographic source:

Curr. Probl. Derm.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Open Epicutaneous Test (OET)

Principles of method if other than guideline:

An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of test chemical

GLP compliance:

not specified

Type of study:

open epicutaneous test

Justification for non-LLNA method:

Currently no LLNA Study is available for assessment.

Test material

Test material information

Constituent 1

Reference substance name:

Phenylacetic acid

EC Number:

203-148-6

EC Name:

Phenylacetic acid

Cas Number:

103-82-2

Molecular formula:

C8H8O2

IUPAC Name:

phenylacetic acid

Test material form:

solid

Details on test material:

- Name of test material: Benzeneacetic acid
- Molecular formula: C8H8O2
- Molecular weight: 136.149 g/mole
- Smiles : c1(ccccc1)CC(O)=O
- Inchl: 1S/C8H8O2/c9-8(10)6-7-4-2-1-3-5-7/h1-5H,6H2,(H,9,10)
- Substance type: Organic
- Physical state: solid

In vivo test system

Test animals

Species:

guinea pig

Strain:

not specified

Sex:

male/female

Details on test animals and environmental conditions:

- Weight at study initiation: 300-450g

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, open

Vehicle:

other: ethanol, acetone, H20, petroleum, PEG and/or other suitable vehicles

Concentration / amount:

Concentration:100%, 30%, 10%, 3%, 1%, or 0.3% Amount: 0.1ml ethanol in acetone, H20, petroleum, PEG and/or other suitable vehicles

Day(s)/duration:

3 weeks (0-21 days)

Adequacy of induction:

other: The maximal non-irritating and the minimal irritating concentrations after repeated applications are determined by the same all-or-none criterion

Challenge

No.:

#1

Route:

epicutaneous, open

Vehicle:

other: ethanol, acetone, H20, petroleum, PEG and/or other suitable vehicles

Concentration / amount:

Concentration:2%
Amount: 0.025ml

Day(s)/duration:

days 21 and 35

Adequacy of challenge:

not specified

No. of animals per dose:

experimental groups of at least 6 guinea pigs for every concentration group
controls 10 guinea pigs were 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 concentration 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. The estimation of the threshold concentration (minimal irritating and maximal nonirritating concentration) is essential for the evaluation of the allergenic capacity of the test material.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 21
- Exposure period:24 hours
- Test groups:6-8 guinea pigs
- Control group:3 guinea pigs
- Site: an area measuring 8 cm2 on the clipped flank skin of the guinea pigs
- Frequency of applications: The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks
- Duration: 21 days (3 weeks)
- Concentrations: 100%, 30%, 10%, 3%, 1%, or 0.3% in vehicle.
Amount: 0.1ml

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: on days 21 and 35
- Exposure period:24 hours
- Test groups: 6-8 guinea pigs
- Control group: 3 guinea pigs
- Site: contralateral flank measuring 2 cm2
- Concentrations: Concentration:2%
Amount: 0.025ml
- Evaluation (hr after challenge): 24,48 and/or 72h.

Challenge controls:

Yes concurrent vehicle.

Positive control substance(s):

not specified

Results and discussion

In vivo (non-LLNA)

Results

Key result

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

2% (0.025ml)

No. with + reactions:

0

Total no. in group:

8

Clinical observations:

No known signs of skin sensitization were observed

Remarks on result:

no indication of skin sensitisation

Any other information on results incl. tables

CAS RN	Maximum user concentration %	Sensitization procedure
		Human		Guinea pigs
		Concentration %	HMT or RIPT	OET
101-41-7	0.2	2	-	-

Applicant's summary and conclusion

Interpretation of results:

other: not sensitizing

Conclusions:

It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 2%. Thus the test chemical was considered to be not sensitizing on skin of guinea pigs at concentration of 2% in an Open Epicutaneous Test (OET).

Executive summary:

An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of test chemical.

 

On day 1 during induction, 0.1 ml of the test chemical was applied at concentrations of 100%, 30%, 10%, 3%, 1%, or 0.3% in vehicle to an area measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, can be read 24 h after each application, or at the end of each week.

 

To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days, as well as 10 untreated, or only pretreated with the vehicle, controls are tested on days 21 and 35 on the contralateral flank with the test material. This test was performed by applying with a pipette 0.025 ml of each concentration to skin areas measuring 2 cm2. The reactions were read after 24,48 and/or 72h.

 

It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 2%.Thus the test chemicalwas considered to be not sensitizing on skin of guinea pigs at concentration of 2% in an Open Epicutaneous Test (OET).