Tris(trimethylsilyl) phosphate

Endpoint summary

Description of key information

Skin Corrosion: Category 1(OECD431/GLP)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted: 14 June 2019 (OECD, 2019)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and lot/batch number of test material:
supplied by Sponsor /Batch number:N200611031


- Purity, including information on contaminants, isomers, etc.: >=98.50%


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Refrigeration (+2 to +8°C)

Test system:

human skin model

Source species:

other: a three dimensional Reconstructed Human Epidermis model

Cell type:

non-transformed keratinocytes

Cell source:

other: cultured on a collagen matrix at the air liquid interface

Justification for test system used:

The assessment of skin corrosivity has typically involved the use of laboratory animals (OECD TG 404). In relation to animal welfare concerns, TG 404 recommends the use of a tiered testing strategy for the determination of skin corrosion and irritation which includes the use of validated in vitro or ex vivo test methods avoiding pain and suffering of animals.

One of the validated in vitro test methods adopted by the OECD TG 431 makes use of reconstructed human epidermis (RhE). The test is designed to predict and classify the skin corrosivity potential of a test item by assessment of its effect on a reconstituted human epidermis, based on the experience that corrosive substances show cytotoxic effects following short-term exposure of the stratum corneum of the epidermis.

Vehicle:

unchanged (no vehicle)

Details on test system:

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: at room temperature
- Temperature of post-treatment incubation (if applicable): 37°C

REMOVAL OF TEST MATERIAL AND CONTROLS
After the respective incubation periods, at room temperature, the epidermis units were removed from the wells and thoroughly rinsed with PBS placed on an absorbent paper to remove excess PBS. The epidermis units were then placed in a 12-well plate filled with 2 mL pre-warmed assay medium to rinse.

After rinsing, each of these epidermal units was gently tapped on an absorbent paper to remove excess assay medium.


DYE BINDING METHOD
- Dye used in the dye-binding assay: [ MTT ]
- Spectrophotometer: Microplate reader Flex Station
- Wavelength: 570 nm

NUMBER OF INDEPENDENT TESTING RUNS / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1
PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)

< 35 % after 3 min exposure Corrosive • Optional sub-category 1A*
≥ 35 % after 3 min exposure AND < 35 % after 60 min exposure OR ≥ 35 % after 60 min exposure AND < 35 % after 240 min exposure Corrosive • A combination of optional Sub-categories 1B and 1C
≥ 35 % after 240 min exposure Non-Corrosive

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 μL


NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 50 μL
- Concentration (if solution): Sodium chloride (NaCl) 0.9% (w/v)

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 50 μL

Duration of treatment / exposure:

240 mins

Duration of post-treatment incubation (if applicable):

3 hour

Number of replicates:

2

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

1

Value:

8.05

Vehicle controls validity:

not examined

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

- OTHER EFFECTS:

- Direct-MTT reduction: Since, the color of MTT solution did not turn to either blue or purple, it was concluded that, the test item did not interact with MTT.
- Colour interference with MTT: Similarly, the water control tested did not show any coloring potential nor did it reduce the MTT.

DEMONSTRATION OF TECHNICAL PROFICIENCY:

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: It is considered that the NC meets the acceptance, if the mean OD value of the 2 tissues is ≥ 0.6 and ≤ 1.5 for every exposure time.
- Acceptance criteria met for positive control: It is considered that the Positive Control (glacial Glacial acetic acid) meets the acceptance if the mean viability expressed as % of the NC, is ≤ 20%.
- Acceptance criteria met for variability between replicate measurements: the difference of viability between the two tissue replicates should not exceed 30%

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

The tissue viability is < 35% after the 60 and 240 minutes exposure, the test item Tris(trimethylsilyl) phosphate is predicted to be corrosive under the experimental conditions described in the report.

Executive summary:

 

In a in vitro skin corrosion study ( G20748) according to OECD 431 TG under GLP compliance, a three dimensional Reconstructed Human Epidermis model were exposed to 50 μL of  Tris(trimethylsilyl) phosphate for 3, 60 and 240 minutes. Skin corrosion is expressed as the remaining cell viability after exposure to the test item. The relative mean tissue viability obtained after the respective treatment periods with the test item was compared to the negative control tissues.

 

The relative mean tissue viability obtained after 3, 60 and 240 minutes treatment duration with the test item compared to the negative control tissues was 98.79, 12.54 and 8.05 %, respectively.The positive control had a mean cell viability of 6.23 % after 240 minutes exposure. The absolute mean OD570of the negative control tissues was within the laboratory historical control data range.

 

In this study, the test item Tris(trimethylsilyl) phosphate is classified as skin corrosive category1 based on GHS criteria.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion:

The skin corrosion potential of Tris(trimethylsilyl) phosphate has been evaluated in one in vitro skin corrosion test using Reconstructed Human Epidermis (RhE) as the test system.

 

In a in vitro skin corrosion study ( G20748) according to OECD 431 TG under GLP compliance, a three dimensional Reconstructed Human Epidermis model were exposed to 50 μL of  Tris(trimethylsilyl) phosphate for 3, 60 and 240 minutes. Skin corrosion is expressed as the remaining cell viability after exposure to the test item. The relative mean tissue viability obtained after the respective treatment periods with the test item was compared to the negative control tissues.

 

The relative mean tissue viability obtained after 3, 60 and 240 minutes treatment duration with the test item compared to the negative control tissues was 98.79, 12.54 and 8.05 %, respectively.The positive control had a mean cell viability of 6.23 % after 240 minutes exposure. The absolute mean OD570of the negative control tissues was within the laboratory historical control data range.

 

In this study, the test item Tris(trimethylsilyl) phosphate is classified as skin corrosive category1 based on GHS criteria.

Eye irritation:

There is no such a study to evalute the eye irritaion potential of Tris(trimethylsilyl) phosphate as it has been waiverd due to the corrision property of the test item.

Justification for classification or non-classification

Based on the available information in the dossier, the substance Tris(trimethylsilyl) phosphate (CAS No.10491-05-9) needs to be classified  for skin corrosion Category 1 and eye damage Category 1 when considering the criteria outlined in Annex I of 1272/2008/EC.