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Skin sensitisation

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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
22 July 2010
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Version / remarks:
March 2003
Deviations:
no
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

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
Molecular formula:
not applicable for UVCB
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
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)

Resultsopen allclose all
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
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
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
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.