Tris(trimethylsilyl) phosphate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2019

Reliability:

1 (reliable without restriction)

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

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(trimethylsilyl) Phosphate
Lot Number DV1105A19028
CAS No 10497-05-9
EINECS-No 234-028-1
Molecular Formula C9H27O4PSi3
Molecular Weight 314.54
Purity 99.60%
Appearance Colorless, clear liquid
Composition Single component
Homogeneity Not stated
Storage Room temperature (20 ± 5 °C)
Test Item Handling and Storage According to SOPA-00147-BIO, Test and Reference Items

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Age at First Dose 8-9 weeks; female animals were non-pregnant and nulliparous
Animal Health Health condition of animals was examined by a veterinarian before initiation of the study.
Acclimation The animals were acclimated under the conditions identical to the conditions during the experiment 5 days prior to the start of treatment. The acclimation was according to the standard operation procedure.
Housing Condition The animals were housed in plastic cages suspended on stainless steel racks, 3 animals per cage in a room equipped with central air-conditioning. The average room temperature was maintained within the range of 22 ± 3°C, relative humidity within 50-60 %. The light regimen was set to a 12-hour light /12-hour dark cycle. The sanitation was performed according to the standard operation procedures.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Doses:

The starting dose could be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg body weight.

No. of animals per sex per dose:

One group of 3 females was dosed in a first step. The test item in limit dose caused mortality of two animals within the first day after administration and the third animal died on the second day. In a second step, 3 females were treated at dose of 300 mg/kg body weight. Test item-related mortality was not observed for 48 hours and therefore, in a third step, another 3 females were treated at the same dose cap

Details on study design:

The test item Tris(trimethylsilyl) Phosphate administered to 3 females Wistar rats at a limit dose of 2000 mg/kg caused lethargy, dyspnea in all animals immediately after administration and piloerection after 4 hours in animal No 3. Animals No 1 and 2 died within the first day after test item administration. Animal No 3 manifested lethargy, dyspnea and piloerection until the death the second day after administration. During necropsy, no macroscopic findings were observed.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Mortality:

Mortality of 3/3 females at limit dose of 2000 mg/kg body weight was observed.
All (6/6 females) animals survived the dose of 300 mg/kg body weight.

Other findings:

All animals were necropsied. During necropsy, no macroscopic findings were observed.

Any other information on results incl. tables

 Clinical observation

Sex	Dose	ID	Administration  Result	Clinical Observation
♀	2000 mg/kg	1	death	- lethargy and dyspnea immediately, persisted for 4 hours - piloerection after 4 hours after administration - death the first day after administration of the test item
		2	death	- lethargy and dyspnea immediately, persisted for 4 hours - piloerection after 4 hours after administration - death the first day after administration of the test item
		3	death	- lethargy and dyspnea immediately persisted for 4 hours - piloerection after 4 hours after administration; - first day lethargy, piloerection and dyspnea occurred - second day lethargy, piloerection and dyspnea occurred until death of animal (on second day)

Sex	Dose	ID	Administration Result	Clinical Observation
♀	300 mg/kg	4	alive	no signs of intoxication, change of health, nor any other adverse reactions during 24 hours and 14-days observation period
		5	alive	no signs of intoxication, change of health, nor any other adverse reactions during 24 hours and 14-days observation period
		6	alive	- salivation, lethargy and piloerection was observed immediately - lethargy persisted for ½ an hour - piloerection was observed until 2^ndhour after administration
		7	alive	- lethargy was observed immediately and persisted for ½ an hour - sleep was observed ½ an hour after administration
		8	alive	- lethargy was observed immediately
		9	alive	- lethargy was observed immediately

Body Weight

Sex	Dose	ID	Body Weight (g)			Body Weight Difference (g)
			Initial	Week 1	Week 2	Week 1 - Initial	Week 2 - Initial	Week 2 - Week 1
♀	2000 mg/kg	1	213	-	-	-	-	-
		2	201	-	-	-	-	-
		3	206	-	-	-	-	-
♀	300 mg/kg	4	216	246	252	30	36	6
		5	216	246	261	30	45	15
		6	226	245	251	19	25	6
		7	216	233	238	17	22	5
		8	224	245	258	21	34	13
		9	213	236	238	23	25	2

Necropsy Results     

Sex	Dose	ID	Result
♀	2000 mg/kg	1	autolytic changes
		2	autolytic changes
		3	no findings
	300 mg/kg	4	no findings
		5	no findings
		6	no findings
		7	no findings
		8	no findings
		9	no findings

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 of the test item Tris(trimethylsilyl) Phosphate is greater than 300 mg/kg and lower than 2000 mg/kg body weight after single oral administration to Wistar rats.
Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that the test item Tris(trimethylsilyl) Phosphate is classified in GHS Category 4 with a LD50 cut off value 500 mg/kg body weight, after single oral administration to Wistar rats.