1,1,1,3,3,3-hexamethyldisilazane

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980-12-22 to 1981-12-6

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The study was conducted according to an appropriate national standard method which is similar to OECD 475, with acceptable restrictions. The restrictions are that the number of cells used for the determination of mitotic index was not stated, but appeared to be about 100 cells per animal, and the report is less detailed than required by the current guideline. Read-across to the registered substance is considered scientifically justified.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Methodologies in Mutagen Testing (Toxicology & Applied Pharm 22: 269-275, 1972).

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

yes

Remarks:

The number of cells evaluated to determine mitotic index was not stated, but appeared to be less than required by the current guideline. Some details were missing from the report.

GLP compliance:

not specified

Type of assay:

chromosome aberration assay

Test material

Test material information

Constituent 1

Reference substance name:

Hydroxytrimethylsilane

EC Number:

213-914-1

EC Name:

Hydroxytrimethylsilane

Cas Number:

1066-40-6

Molecular formula:

C3H10OSi

IUPAC Name:

Trimethylsilanol

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: Gofmoor Farms

- Age at study initiation: 10 - 16 weeks

- Weight at study initiation: 200 - 280 g

- Assigned to test groups randomly: no information

- Housing: Six per cage

- Diet (e.g. ad libitum): ad libitum

- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS

- Temperature (°F): 68 ± 3 °F

- Humidity (%): approx 50 %

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: DMSO

- Justification for choice of solvent/vehicle: solubility properties

- Lot/batch no. (if required): D-128

- Purity: reagent grade

Details on exposure:

Route of exposure: intraperitoneal

Duration of treatment / exposure:

6 - 48 hours

Frequency of treatment:

A single intraperitoneal administration equivalent to doses of 420, 200 and 100 mg/kg.

Post exposure period:

Animals were sacrificed at 6, 24 or 48 hours after injection.

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
100 mg/kg bw
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
200 mg/kg bw
Basis:
nominal conc.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
420 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

6

Control animals:

yes, concurrent vehicle

Positive control(s):

- cyclophosphamide

- Justification for choice of positive control(s): standard guideline positive control

- Route of administration: intraperitoneal

Examinations

Tissues and cell types examined:

Chromosomes from bone marrow examined for breaks.

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: rang-finding experiment to determine the maximum tolerated dose

DETAILS OF SLIDE PREPARATION: a small amount of cells suspended in fixative (3:1, methanol: acetic acid) were dropped onto slides which were subsequently air dried. Slides were stained with 5 % Giemsa.

METHOD OF ANALYSIS: Slides were scanned and only those of acceptable quality were retained. Suitable cells were photographed using a 100x objective. A minimum of 100 metaphase cells were analyzed per animal, and 5 animals were analysed for each dose.

Evaluation criteria:

The test substance is cytogenic if it causes a statistically significant, dose related increase in the frequency of chromosomal breaks or aberrations.

Statistics:

The significance of differences in break frequency were examined using "goodness to fit" to a Poisson distribution, compared to historical negative control data, the Wilcoxon test and Chi square.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Remarks:

on bone marrow

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY

- Dose range: experiment 1: 175, 500, 1750, 5000 mg/kg bw; experiment 2: 75, 50, 175, 500, 1750 mg/kg bw

- Clinical signs of toxicity in test animals: none reported. Deaths occurred at the top dose in experiment 1 and in the top two doses in experiment 2.

Any other information on results incl. tables

Table 1: Results of chromosome analysis in Rat Bone Marrow Cells

 

		Solvent Control (DMSO)			Positive Control Cyclophosphamide	Low dose 100 mg/kg			Mid dose 200 mg/kg			High dose 420 mg/kg
Sampling time (h)		6	24	48	24	6	24	48	6	24	48	6*	24	48
Number of cells analysed		551	592	523	286	552	568	502	546	593	509	499	574	534
Toxicity		No	No	No	No	No	No	No	No	No	No	No	No	No
Total number of Chromosome aberrations	Gaps	ND	ND	ND	0	2	7	12	3	5	11	6	5	8
	Breaks	0	2	4	>99	2	7	5	6	3	8	3	5	12
	Interchanges	ND	ND	ND	0	0	0	0	0	0	0	0	0	0
Polyploidy		ND	ND	ND	ND	ND	ND	ND	ND	ND	ND	ND	ND	ND
Endo reduplication		ND	ND	ND	ND	ND	ND	ND	ND	ND	ND	ND	ND	ND

  ND Not determined

 

Applicant's summary and conclusion

Conclusions:

Trimethylsilanol (CAS 1066-40-6) has been tested in chromosome aberration study conducted according to a protocol that is similar to OECD Test Guideline 475. The test substance did not cause a statistically significant, dose related increase in chromosome breaks or aberrations when administered by intraperitoneal injection to Sprague Dawley rats up to the maximum tolerated dose. It is concluded that the test substance is not clastogenic in rat bone marrow cells under the conditions of the test.