Methyl phenylacetate

Endpoint summary

Description of key information

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).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

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

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. 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.

Species:

guinea pig

Strain:

not specified

Sex:

male/female

Details on test animals and environmental conditions:

- Weight at study initiation: 300-450g

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

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

Key result

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

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

CAS RN	Maximum user concentration %	Sensitization procedure
		Human		Guinea pigs
		Concentration %	HMT or RIPT	OET
101-41-7	0.8	8	-	-

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In various studies, the test chemical has been investigated for potential to cause dermal sensitization in living organisms to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs, humans. The results are summarized as follows:

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 chemical was considered to be not sensitizing on skin of guinea pigs at concentration of 2% in an Open Epicutaneous Test (OET).

This is supported by the results of a human maximization test carried out to assess the dermal sensitization potential of the test chemical. The test chemical 8% in petrolatum was applied to the skin of 25 human volunteers and observed for signs of dermal sensitization (duration of exposure, observation period not specified).

The test chemical 8% in petrolatum did not induce any sensitization reactions on the skin of 25 human volunteers.

Hence, the test chemical was considered to be not sensitizing to skin.

Skin sensitization effects were also estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for the test chemical. Based on estimation, no skin sensitization reactions were observed in guinea pigs and humans. Therefore, the test chemical was considered to be not sensitizing.

These results are supported by results of a maximization test carried out with 4% (2760 microgram/cm2) test chemical in petrolatum on 25 healthy male patients. Application was under occlusion to the same site on the forearms of all subjects for five alternate day, 48 h periods. The patch sites were pretreated for 24 hours with 5% aqueous sodium lauryl sulfate (SLS) under occlusion. Following a 10 day rest period, challenge patches were applied to fresh sites on the back for 48 h under occlusion. The challenge site was pre-treated for 1 hour with 10% SLS. The challenge site was evaluated at 48 and 72 hours. No sensitization reactions were observed after the challenge exposure. Hence, the test chemical was considered to be not sensitizing to skin.

The above results are further supported by the results of a human maximization test carried out to assess the dermal sensitization potential of the test chemical in humans. The test chemical was applied in concentration 2% in petrolatum to the skin of 25 human volunteers and observed for signs of dermal irritation or sensitization.

No sensitization reactions were observed in any of the volunteers. Hence, the test chemical can be considered to be not sensitizing to human skin.

Based on the results obtained, the test chemical can be considered to be not sensitizing to skin.Comparing the above annotations with the criteria of CLP regulation, the test chemical can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

 

Available data for the test chemical indicates that it is not likely to induce any dermal reactions.

Hence, the test chemical can be considered to be not sensitizing to skin.