Reaction mass of phosphonic acid, methyl-, bis[(5-ethyl-2-methyl-2,2-dioxido-1,3,2-dioxaphosphorinan-5-yl)methyl] ester with (5-ethyl-2-methyl-2-oxido-1,3,2-dioxaphosphorinan-5-yl)methyl methyl methylphosphonate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26-08-2015 until 29-09-2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

22 July 2010

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Version / remarks:

March 2003

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

6 July 2012

Deviations:

no

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:

Reaction mass of phosphonic acid, methyl-, bis[(5-ethyl-2-methyl-2,2-dioxido-1,3,2-dioxaphosphorinan-5-yl)methyl] ester with (5-ethyl-2-methyl-2-oxido-1,3,2-dioxaphosphorinan-5-yl)methyl methyl methylphosphonate

EC Number:

915-680-2

Cas Number:

170836-68-7

Molecular formula:

not applicable for UVCB substance

IUPAC Name:

Reaction mass of phosphonic acid, methyl-, bis[(5-ethyl-2-methyl-2,2-dioxido-1,3,2-dioxaphosphorinan-5-yl)methyl] ester with (5-ethyl-2-methyl-2-oxido-1,3,2-dioxaphosphorinan-5-yl)methyl methyl methylphosphonate

Test material form:

liquid

Specific details on test material used for the study:

Commercial name: AFLAMMIT® PE CONC
Batch number: RP-324566-1512
Chemical Name: Mixture of CAS 42595-45-9 and CAS 41203-81-0 (cyclic phosphonate esters)

In vivo test system

Test animals

Species:

mouse

Strain:

CBA/Ca

Remarks:

CBA/CaOlaHsd mice, Source: Harlan Laboratories S.r.l., Italy

Sex:

female

Study design: in vivo (LLNA)

Vehicle:

other: 1% aqueous Pluronic PE9200

Concentration:

test item concentrations of 50, 25 or 10% (w/v) in 1% Pluronic, corresponding to
46.75 %, 23.375 % or 9.35 % active ingredient, respectively

No. of animals per dose:

5

Details on study design:

per guideline

Positive control substance(s):

other: 25 % (w/v) HCA (dissolved in 1% Pluronic)

Results and discussion

Positive control results:

The result of the positive control substance α-Hexylcinnamaldehyde (HCA) dissolved in
the same vehicle was used to demonstrate the appropriate performance of the assay [1]. A
significant lymphoproliferative response (stimulation index value of 8.8) was noted for the
positive control chemical, this result confirmed the validity of the assay.

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Remarks:

50% (w/v)

Value:

1.7

Test group / Remarks:

Test group SI values were not significantly different from (vehicle) control (Mann-Whitney U-test versus negative control)

Remarks on result:

other: no indication of skin sensitisation

Results 2

Key result

Parameter:

SI

Remarks:

25% (w/v)

Value:

1.1

Test group / Remarks:

Test group SI values were not significantly different from (vehicle) control (Mann-Whitney U-test versus negative control)

Remarks on result:

other: no indication of skin sensitisation

Results 3

Key result

Parameter:

SI

Value:

0.9

Test group / Remarks:

Test group SI values were not significantly different from (vehicle) control (Mann-Whitney U-test versus negative control)

Remarks on result:

other: no indication of skin sensitisation

Results 4

Parameter:

EC3

Value:

0

Remarks on result:

not determinable

Cellular proliferation data / Observations:

The appearance of the lymph nodes was normal in all test item treated dose groups except one animal (Animal No.: 9896); this animal had slightly enlarged lymph nodes. Larger than normal lymph nodes were observed in the positive control group.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present Local Lymph Node Assay the test item (technical product of cyclic phosphonates), tested in a suitable vehicle, was shown to have no sensitisation potential (non-sensitiser).

Executive summary:

To assess the skin sensitising potential of the test item (technical product of cyclic phosphonates)

a Mouse Local Lymph Node Assay has been performed in accordance with GLP requirements.

Groups of five animals each received either the test item formulated in 1% Pluronic at 50, 25, and

10 % (w/v) concentrations or the vehicle (negative control), or 25 % (w/v) HCA (positive control).

No mortality or systemic clinical signs were observed during the study. No treatment

related effects were observed on the mean body weight changes, however marked body

weight loss (>5%) was observed for one animal in the 10 % (w/v) dose group. There were

no indications of any irritancy at the site of application.

The observed stimulation index values were 1.7, 1.1 and 0.9 at concentrations of 50, 25 and

10 % (w/v), respectively.

The result of the positive control substance α-Hexylcinnamaldehyde (HCA) dissolved in

the same vehicle was used to demonstrate the appropriate performance of the assay [1]. A

significant lymphoproliferative response (stimulation index value of 8.8) was noted for the

positive control chemical, this result confirmed the validity of the assay.

In conclusion, under the conditions of the present assay the test item,

tested in a suitable vehicle, was shown to have no sensitisation potential (nonsensitiser)

in the Local Lymph Node Assay.