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Toxicological information

Skin sensitisation

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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 reviwed journals

Data source

Reference
Reference Type:
publication
Title:
The Freund's Complete Adjuvant Test and the Open Epicutaneous Test
Author:
G. Klecak
Year:
1985
Bibliographic source:
Curr. Probl. Derm., vol.14, pp.152-171 (Karger, Basel 1985)

Materials and methods

Test guideline
Qualifier:
according to
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. The Guinea Pig Maximization Test (GPMT) has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): methyl phenylacetate
- Molecular Formula: C9H10O2
- Molecular Weight: 150.176 g/mol
- Substance type: Organic
- Physical state: Liquid

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:
100%, 30%, 10%, 3%, 1%, or 0.3%
Day(s)/duration:
3 weeks
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:
0.025 ml of 2%
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.
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 group
Dose level:
0.025 ml
No. with + reactions:
0
Total no. in group:
6
Clinical observations:
no dermal reactions 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

0.8

8

-

-

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).