Tris(trimethylsilyl) phosphate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

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 429 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Tris(trimethylsilyl) phosphate

EC Number:

234-028-1

EC Name:

Tris(trimethylsilyl) phosphate

Cas Number:

10497-05-9

Molecular formula:

C9H27O4PSi3

IUPAC Name:

tritrimethylsilyl phosphate

Specific details on test material used for the study:

Test Item Tris(trimethysilyl) Phosphate
Batch Number DV1105A19028
EC Number 234-028-1
CAS Number 10497-05-9
Appearance Colorless, clear liquid
Composition Single component
Purity 99.60 %
Molecular Formula C9H27O4PSi3
Storage Room Temperature: 20 ± 5 ° C

In vivo test system

Test animals

Species:

mouse

Strain:

CBA/Ca

Sex:

female

Details on test animals and environmental conditions:

Age at First Dose 8-10 weeks, female animals were non-pregnant and nulliparous were used
Animal Health The health condition and skin integrity of animals was examined by a veterinarian before initiation of the study. Animals were healthy, without visible signs of disease and skin lesions.
Acclimation The animals were acclimated in identical conditions as during the experiment for 5 days prior to the start of treatment. The acclimation was according to standard operation procedures.
Housing Condition The animals were housed in IVC polycarbonate cages (5 animals per cage) suspended on stainless steel racks, in a room equipped with central air-conditioning. The room temperature was within the range of 22 ± 3°C, relative humidity was at least of 30 % and did not exceed 70 %, the aim was 50-60 %. The light regimen was set to a 12-hour light / 12-hour dark cycle. The sanitation was performed according to standard operation procedures.

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

The doses were selected from the concentration series 100 %, 50 %, 25 %, 10 %, 5 %, 2.5 % etc. according to OECD Guideline No. 429.

No. of animals per dose:

Negative control (vehicle) group - 5 females
Positive control group - 5 females
Test item groups - 15 females (3 concentrations, 5 animals per concentration)
Pre-screen test - 4 females (2 animals per group)

Details on study design:

Pre-screen test
The pre-screen test was conducted under the same conditions as the main LLNA study, except for the assessment of lymph node proliferation.
Test procedure of Pre-screen test
All mice (2 mice/group) were observed daily for any clinical signs of toxicity or local irritation at the application site. Body weights were recorded pre-test and prior to the termination (day 6). Both ears of each mouse were assessed for any signs of irritation. Erythema scores are shown in table 1. Ear thickness was measured by a calliper on Day 1 (pre-dose), Day 3 and Day 6. Excessive local skin irritation is indicated by an erythema score ≥ 3 and/or an increase in ear thickness of ≥ 25 %.
Main study
Day 1:
Each animal was identified and the body weight was recorded. To the dorsum of each ear, 25 µL of the appropriate dilution of the test item, or the vehicle alone was applied.
Days 2 and 3:
The application procedure carried out on day 1 was repeated.
Days 4 and 5: No treatment.
Day 6:
The body weight of each animal was recorded. 250 µL of sterile phosphate-buffered saline (PBS) containing 2 µCi (7.4 x 104 Bq) of 125I-iododeoxyuridine and 10-5M fluorodeoxyuridine was injected into all test and control mice via the tail vein.
Five hours later, the animals were sacrificed. The draining auricular lymph nodes from each ear were excised and pooled in PBS for each experimental group (pooled treatment group approach).

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

ca. 0.63

Test group / Remarks:

Tris(trimethysilyl) Phosphate 10 %

Results 2

Key result

Parameter:

SI

Value:

ca. 1.8

Test group / Remarks:

Tris(trimethysilyl) Phosphate 25 %

Results 3

Key result

Parameter:

SI

Value:

ca. 2.78

Test group / Remarks:

Tris(trimethysilyl) Phosphate 50 %

Cellular proliferation data / Observations:

Animals were carefully observed for any clinical symptoms, either of local irritation at the application site or systemic toxicity. The daily clinical observation of the animals did not show visible clinical signs of toxicity.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The skin sensitization potential of Tris(trimethysilyl) Phosphate was evaluated by LLNA method, basic underlying principle of the LLNA method is that sensitizers induce a primary proliferation of lymphocytes in the auricular lymph nodes draining the site of chemical application.
In the present study, the test item was applied to the dorsum of each ear of five female mice (CBA/Ca) per group over three consecutive days, at three concentrations (10 %, 25 % and 50 % v/v). All animals survived throughout the test period without showing any clinical signs of toxicity.
The EC3 value could not be calculated, since none of the tested concentrations induced a S.I. was not greater than the threshold value of 3.
These results demonstrate that Tris(trimethysilyl) Phosphate is not considered a skin sensitizer under the test conditions of this study.