Methyl anthranilate

Endpoint summary

Description of key information

No dermal reactions were observed on the skin of the volunteers. Therefore, the test chemical was considered to be not sensitizing to humans. Hence, the test chemical can be classified under the category "Not Classified" as per CLP Regulation.

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 reviewed journal.

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

To evaluate the skin sensitizing potential of the test chemical in Human by Human Maximisation test.

GLP compliance:

not specified

Type of study:

other: Human Maximisation test.

Justification for non-LLNA method:

no data available

Species:

other: Human

Strain:

other: Not applicable.

Sex:

not specified

Details on test animals and environmental conditions:

Age: the preferred age range is 18 to 50 years.

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

10%

Day(s)/duration:

48 hours

Adequacy of induction:

other: 1.0 ml of 5% aqueous sodium lauryl sulfate (SLS) was applied to a 1.5 inch square of Webril under occlusive conditons for 24 hours.

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

10%

Day(s)/duration:

48 hours

Adequacy of challenge:

other: A provocative patch test consists of pre-treating the skin occlusively with 0.4 ml of 10% SLS on a 1.0" Webril square for one hour.

No. of animals per dose:

Group 1: 24 human volunteers
Group 2: 26 human volunteers

Details on study design:

RANGE FINDING TESTS: no data available

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: total 5 exposures
- Exposure period: 48 hours
- Test groups: 2 (24 and 26)
- Control group: No data available.
- Site: forearm or back
- Frequency of applications: The procedure consists of five 48 hour exposures, each one preceded by a 24 hour pre-treatment with 5% SLS..
- Duration: 2 weeks
- Concentrations: 10% in petrolatum

B. CHALLENGE EXPOSURE
- No. of exposures: single
- Day(s) of challenge:
- Exposure period: 48 hours
- Test groups: 2 (24 and 26)
- Control group: A control patch was necessary for the provocative test consisting of petrolatum applied for 48 hours to a site pretreated for one hour with 10% aqueous sodium lauryl sulfate.The allergen treated site was not regarded as positive unless it was clearly more inflammatory than the control site.
- Site: forearm or back
- Concentrations: 10% in petrolatum
- Evaluation (hr after challenge): The challenge reaction was read immediately after removal of the 48 hour patch and again in another two days

Challenge controls:

A control patch was necessary for the provocative test consisting of petrolatum applied for 48 hours to a site pretreated for one hour with 10% aqueous sodium lauryl sulfate.The allergen treated site was not regarded as positive unless it was clearly more inflammatory than the control site.

Positive control substance(s):

not specified

Positive control results:

No data available

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10% in Petrolatum

No. with + reactions:

0

Total no. in group:

24

Clinical observations:

No skin sensitization reaction observed.

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10% in petrolatum

No. with + reactions:

0

Total no. in group:

26

Clinical observations:

No skin sensitization reaction

Remarks on result:

no indication of skin sensitisation

No skin sensitization reaction observed.

Interpretation of results:

other: Not sensitizing.

Conclusions:

No dermal reactions were observed on the skin of the volunteers. Therefore, the test chemical was considered to be not sensitizing to humans. Hence, the test chemical can be classified under the category "Not Classified" as per CLP Regulation.

Executive summary:

A human maximization study was performed to assess the dermal sensitization potential of the test chemical. During the induction exposure, the sensitizing patches were applied to an extremity, either the forearm or the lower leg in the calf region. The entire series of patches were applied to exactly the same site. The procedure was as follows: 1.0 ml of 5% aqueous sodium lauryl sulfate (SLS) was injected on to the Webril patches and fastened to an extremity under occlusive conditions for 24 hours. To the same site, a 48 hour occlusive patch with 10% test chemical in petrolatum was applied to the skin of 24 and 26 human volunteers. The procedure of alternating 24 hour irritant i.e 24 hour pre-treatment with 5% SLS and 48 hour allergen patches were repeated for a total of five exposures. After a suitable rest period, the challenge exposure was performed. Before conducting the challenge test, a "SLS provocative patch test," was performed at the test site. A provocative patch test consisted of pre-treating the skin occlusively with 0.4 ml of 10% SLS on a 1.0 inch Webril square for one hour. After provocative patch test, the test chemical patches were applied under occlusive conditions on the same site for 48 hours. The challenge reactions were read immediately after removal of the 48 hours patch and again in another two days. An evident erythema was regarded as the minimum positive response. No dermal reactions were observed on the skin of the volunteers. Therefore, the test chemical was considered to be not sensitizing to humans. Hence, the test chemical can be classified under the category "Not Classified" as per CLP Regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Following studies were conducted to determine the toxic nature of test chemical:

A human maximization study was performed to assess the dermal sensitization potential of the test chemical. During the induction exposure, the sensitizing patches were applied to an extremity, either the forearm or the lower leg in the calf region. The entire series of patches were applied to exactly the same site. The procedure was as follows: 1.0 ml of 5% aqueous sodium lauryl sulfate (SLS) was injected on to the Webril patches and fastened to an extremity under occlusive conditions for 24 hours. To the same site, a 48 hour occlusive patch with 10% test chemical in petrolatum was applied to the skin of 24 and 26 human volunteers. The procedure of alternating 24 hour irritant i.e 24 hour pre-treatment with 5% SLS and 48 hour allergen patches were repeated for a total of five exposures. After a suitable rest period, the challenge exposure was performed. Before conducting the challenge test, a "SLS provocative patch test," was performed at the test site. A provocative patch test consisted of pre-treating the skin occlusively with 0.4 ml of 10% SLS on a 1.0 inch Webril square for one hour. After provocative patch test, the test chemical patches were applied under occlusive conditions on the same site for 48 hours. The challenge reactions were read immediately after removal of the 48 hours patch and again in another two days. An evident erythema was regarded as the minimum positive response. No dermal reactions were observed on the skin of the volunteers. Therefore, the test chemical was considered to be not sensitizing to humans. Hence, the test chemical can be classified under the category "Not Classified" as per CLP Regulation.

An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of test chemical. The pretest was performed to determine the primary irritating threshold concentration of test substances at various concentrations (e.g, 100,30,10 and 3%). In this test, a single application of 0.025 ml of each test concentration was 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. On the basis of pretest, the concentration selected for sensitization test was 10%. On day 1 during induction, 0.1 ml of the test chemical was applied at concentrations of 10% 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 chemical 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 10%.Thus, the chemical was considered to be not sensitizing on skin of guinea pigs at concentration of 10% in an Open Epicutaneous Test (OET).

Based on the available data for the test chemical, it can be concluded that the target chemical is not sensitizing in nature. Therefore the target chemical was estimated to be not sensitizing to skin and it can be further classified under the category “Not Classified” as per CLP regulation.

Justification for classification or non-classification

Based on the above studies of test chemical, it can be concluded that no dermal reactions were observed. Thus, caccording CLP regulation, the given test chemical cannot be classified for Skin Sensitization toxicity.