Propan-2-yl N-[(S)-(pentafluorophenoxy)(phenoxy) phosphoryl]-L-alaninate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 November 2012-22 November 2013

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Propan-2-yl N-[(S)-(pentafluorophenoxy)(phenoxy)-phosphoryl]-L-alanine

EC Number:

695-076-0

Cas Number:

1334513-02-8

Molecular formula:

C18H17F5NO5P

IUPAC Name:

Propan-2-yl N-[(S)-(pentafluorophenoxy)(phenoxy)-phosphoryl]-L-alanine

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Test item
- Name of test material (as cited in study report): GS-606962
- Substance type: organic
- Physical state: white powder
- Lot/batch No.: PSI-172(2)-1-1-12001
- Date received: 09 July 2012
- Storage condition of test material: room temperature in the dark

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

2.5, 5, 10 % w/w

No. of animals per dose:

Three groups of four animals

Results and discussion

In vivo (LLNA)

Results

Parameter:

SI

Remarks on result:

other: Stimulation index = 2.40 for 2.5 % w/w in acetone/olive oil 4:1 Stimulation index = 3.10 for 5 % w/w in acetone/olive oil 4:1 Stimulation index = 3.81 for 10 % w/w in acetone/olive oil 4:1 EC3 value calculated = 4.6%

Any other information on results incl. tables

The Stimulation Index expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group are as follows:

Concentration (% w/w) in acetone/olive oil 4:1	Stimulation Index	Result
2.5	2.40	Negative
5	3.10	Positive
10	3.81	Positive

The concentration of the test item expected to cause 3 fold increase in ³HTdR incorporation (EC₃ value) was calculated to be 4.6%.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Remarks:

Migrated information

Conclusions:

The test item was considered to be sensitiser under the conditions of the test.

Executive summary:

Introduction

A study was performed to assess the skin sensitisation potential of the test item in the CBA/Ca strain mouse following topical application to the dorsal surface of the ear. The method was designed to be compatible with the following:

- OECD Guideline for the Testing of Chemicals No. 429 "Skin Sensitisation: Local Lymph Node Assay" (adopted 22 July 2010)

- Method B42 Skin Sensitisation (Local Lymph Node Assay) of Commission Regulation (EC) Nà. 440/2008

Methods

Following a preliminary screening test in which no clinical signs of toxicity were noted at a maximum attainable concentration of 10% w/w, this concentration was selected as the highest dose investigated in the main test of the Local Lymph Node Assay. Three groups, each o four animals, were treated with 50 µl (25 µl per ear) of the test item as a solution in acetone/olive oil 4:1 at concentrations of 10%, 5% or 2.5% w/w. A further group of four animals was treated with acetone/olive oil 4:1 alone.

Results

The Stimulation Index expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group are as follows:

Concentration (% w/w) in acetone/olive oil 4:1	Stimulation Index	Result
2.5	2.40	Negative
5	3.10	Positive
10	3.81	Positive

The concentration of the test item expected to cause 3 fold increase in³HTdR incorporation (EC₃value) was calculated to be 4.6%.

Conclusion

The test item was considered to be sensitiser under the conditions of the test.