3-bis(diisopropylamino)phosphanyloxypropanenitrile

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From April 26 2019 to August 16th 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)

Version / remarks:

2018

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

3-({bis[bis(propan-2-yl)amino]phosphanyl}oxy)propanenitrile

EC Number:

600-337-9

Cas Number:

102691-36-1

Molecular formula:

C15H32N3OP

IUPAC Name:

3-({bis[bis(propan-2-yl)amino]phosphanyl}oxy)propanenitrile

Test material form:

liquid

Details on test material:

clear, colourless liquid

Test animals / tissue source

Species:

human

Details on test animals or tissues and environmental conditions:

The EpiOcular tissue construct is a non-keratinized epithelium (0.6 cm2 ) prepared from normal human keratinocytes (MatTek). It models the cornea epithelium with progressively stratified, but not cornified cells. These cells are not transformed or transfected with genes to induce an extended life span in culture. The “tissue” is prepared in inserts with a porous membrane through which the nutrients pass to the cells. A cell suspension is seeded into the insert in specialized medium. After an initial period of submerged culture, the medium is removed from the top of the tissue so that the epithelial surface is in direct contact with the air. This allows the test material to be directly applied to the epithelial surface in a fashion similar to how the corneal epithelium would be exposed in vivo.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

The liquid test item was applied undiluted (50 μL) directly on top of the tissue.

Duration of treatment / exposure:

The tissues were incubated at standard culture conditions for 2 hours.

Number of animals or in vitro replicates:

2 replicates

Results and discussion

In vitro

Results

Irritation parameter:

other: Cell Viability

Value:

ca. 86

Negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In conclusion, The substance is non-irritant in the EpiOcularTM test under the experimental conditions described in this report.

Executive summary:

The objective of this study was to evaluate the eye hazard potential of the substance which was topically applied on the Reconstructed Human EpiOcularTM Model.

The possible eye hazard potential of the substance was tested through topical application for 30 minutes.

The substance was applied undiluted (50 μL) directly on top of the tissue for 30 ± 2 minutes. After exposure the cornea epithelial construct was thoroughly rinsed to remove the test item

and transferred to fresh medium for an immersion incubation. Afterwards, the tissues were transferred to fresh medium and incubated for 2 hours at standard culture conditions, prior to

determination of the cytotoxic (irritancy) effect.

The positive control had a mean cell viability of 23% after 30 ± 2 minutes exposure. The absolute mean OD570 (optical density at 570 nm) of the negative control tissues was within the laboratory historical control data range. The difference between the percentage of viability of two tissues treated identically was less than 9%, indicating that the test system functioned properly.

Eye hazard potential is expressed as the remaining cell viability after exposure to the test item. The relative mean tissue viability obtained after 30 ± 2 minutes treatment with the substance compared to the negative control tissues was 86%.

Since the mean relative tissue viability for the substance was above 60% after 30 ± 2 minutes treatment, the substanceagent is considered to be non-irritant.

In conclusion, The susbtance is potentially non-irritant in the EpiOcularTM test under the experimental conditions.