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 irritation / corrosion

Administrative data

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28-04-2015 - 29-04-2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)

Version / remarks:

September 2014

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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 vitro test system

Test system:

human skin model

Remarks:

SkinEthic™ Reconstructed Human Epidermis

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

other: no data

Source strain:

other: not applicable

Justification for test system used:

The SkinEthic™ skin corrosion test method is a validated alternative test procedure to in vivo skin
corrosion effects assessed in rabbits according the OECD guideline 404 and was endorsed by
OECD guideline 431.

Vehicle:

unchanged (no vehicle)

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

Test materials ( 40 μL liquid) were applied to the RHE tissue (n=2) for 3 minutes and 1 hour at room temperature then rinsed.

Duration of treatment / exposure:

3, 60 minutes

Duration of post-treatment incubation (if applicable):

none

Number of replicates:

2 and 2

Results and discussion

In vitro

Results

Results 1

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

3 min

Value:

100

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Results 2

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

60 min

Value:

90.8

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Other effects / acceptance of results:

Assay Acceptance Criterion 1:
Negative Control viability meets the acceptance criterion.

Assay Acceptance Criterion 2:
Positive Control viability meets the acceptance criterion.

Assay Acceptance Criterion 3: Coefficient of Variation (CV)
The experiments were performed on two tissue replicates per exposure time and difference of
viability between the two tissue replicates not exceed 30% (in the range 20-100% viability, and
for ODs ~ 0.3).

Tiered test for direct MTT reduction
The MTT tiered test ensures that there is not direct interaction between the test sample and MTT
and therefore corrects against chemicals which might otherwise be falsely predicted as noncorrosive.
If interaction is observed, the test substances are applied to freeze killed controlled
tissue to determine the likelihood of the interaction occurring under test conditions.
40 μL of AFLAMMIT® PE CONC was incubated with MTT for 3 hours. There was no visual
evidence of MTT reduction (violet coloration). Therefore application onto freeze killed tissue was
not required.

Batch release quality control
The tissue batch n°15 RHE 054 met the acceptance criteria defined into the certificate of analysis.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The viability of the RHE in the presence of the test item (technical product of cyclic phosphonates) was above 50% at 3 minutes
and was above 15% after 1 hour exposure, following analysis by the MTT viability assay.
Therefore, the sample was classified as non corrosive.

Executive summary:

The corrosive potential of the test item (technical product of cyclic phosphonates) was tested using the SkinEthic™ RHE model (OECD 431, GLP) and expressed as a percent of the negative control tissue NC (water).

The viability of the RHE in the presence of the test item was 100% ± 6% (criterium: above 50%) at 3 minutes and was 90.8 ± 6% (critrium: above 15%) after 1 hour exposure, following analysis by the MTT viability assay.

Therefore, the sample was classified as non corrosive.