Trimethoxy(2,4,4-trimethylpentyl)silane

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 Nov 2000 to 15 Jan 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

BAYERISCHES LANDESAMT FÜR ARBEITSSCHUTZ, ARBEITSMEDIZIN UND SICHERHEITSTECHNIK, München, Germany

Type of assay:

other: micronucleus assay (chromosome aberration)

Test material

Test material information

Constituent 1

Reference substance name:

Triethoxy(2,4,4-trimethylpentyl)silane

EC Number:

252-558-1

EC Name:

Triethoxy(2,4,4-trimethylpentyl)silane

Cas Number:

35435-21-3

Molecular formula:

C14H32O3Si

IUPAC Name:

triethoxy(2,4,4-trimethylpentyl)silane

Details on test material:

- Name of test material (as cited in study report): Wacker BS 1701
- Physical state: Liquid
- Lot/batch No.: KH 02343
- Expiration date of the lot/batch: November 2001
- Stability under test conditions: stable in aqueous solution for at least 24 h
- Storage condition of test material: at room temperature, protected from light

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelman (D-33178, Borchen)
- Weight at study initiation: 24-42 g
- Assigned to test groups randomly: yes, under following basis: assigned and tail tagged by chance
- Housing: Macrolon Type III (Hereto, D-79302 Emmendingen)
- Diet: pelleted standard diet (ALTROMIN, Lage/Lippe, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 49.5-61
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

- Vehicle(s)/solvent(s) used: CMC (carboxymethyl cellulose)
- Justification for choice of solvent/vehicle: The vehicle was chosen because it is relatively non toxic to the test animals
- Lot/batch no. (if required): 36H0738

Details on exposure:

Route of exposure: Oral

Duration of treatment / exposure:

24-48 h

Frequency of treatment:

The animals received the test item once orally.

Post exposure period:

Animals were sacrificed 24-48 h after treatment.

Doses / concentrations

Dose / conc.:

2 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

- cyclophosphamide
- Justification for choice of positive control(s): standard guideline positive control
- Route of administration: oral
- Doses / concentrations: 10 ml/kg bw of 0.9% solution in 0.9% NaCl

Examinations

Tissues and cell types examined:

Bone marrow, erythrocytes

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: limit dose

DETAILS OF SLIDE PREPARATION: centrifuged cells were suspended in a thin layer of FCS and smeared on a slide. The smears were air dried and stained with May-Gruenwald (Merck, D-64293 Darmstadt)/Giemsa (Merck, D-64293 Darmstadt).

METHOD OF ANALYSIS: microscopic examination. 2000 PCE scored for incidence of polychromatic erythrocytes with micronuclei. Ratio of PCE / NCE was scored based on 1000 erythrocytes (PCE+NCE)

Evaluation criteria:

A test item is classified as mutagenic if it induces either a statistically significant dose related increase in the number of micronucleated polychromatic erythrocytes or a reproducible statistically significant positive response for at least one of the test points.

Statistics:

Micronuclei in 2000 PCE per animal were counted for each sex. NCE per 1000 PCE, Sum and Mean calculated for each sex.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

See table 3

RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): negative
- Ratio of PCE/NCE (for Micronucleus assay): see table 3. The PCE/NCE ratio was unchanged in treated animals, so there is no evidence that the test substance reached the target tissue.
- Appropriateness of dose levels and route: appropriate dose and route
- Statistical evaluation: no statistically significant induction of micronuclei occurred.

Any other information on results incl. tables

Table 3: Results of in vivo micronucleus test

		Vehicle Control	Positive Control	200 mg/kg bw	1000 mg/kg bw	2000 mg/kg bw	2000 mg/kg bw
Number of cells evaluated		2000	2000	2000	2000	2000	2000
Sampling time (h)		24	24	24	24	24	48
Number of erythrocytes	normo­chromatic	NR	NR	NR	NR	NR	NR
	poly­chromatic	2000	2000	2000	2000	2000	2000
	polychromatic with micronuclei	7 Male 5.2 Female	70.2 Male 42.4 Female	7.6 Male 9.2 Female	8.4 Male 4.8 Female	9.4 Male 5.0 Female	7.4 Male 4.8 Female
Ratio of erythrocytes	polychromatic / normochromatic	Male 1000/679.4 Female 1000/766.6	Male 1000/608 Female 1000/657.6	Male 1000/712.4 Female 1000/655.8	Male 1000/656.4 Female 1000/611.6	Male 1000/657 Female 1000/641.2	Male 1000/1064.6 Female 1000/511
	polychromatic with micro­nuclei / normochromatic	NR	NR	NR	NR	NR	NR

 NR = not required

Applicant's summary and conclusion

Conclusions:

Interpretation of results: negative
The test item has been tested in a reliable in vivo mouse micronucleus assay according to OECD TG 474 and in compliance with GLP. No statistically significant increase in the number of cells with micronuclei was observed after oral administration up to the limit dose of 2000 mg/kg bw. Appropriate positive and vehicle controls were included and gave expected results. The PCE / NCE ratio was slightly affected in treated males, indicating that the test item was of low toxicity to the target tissue. It is concluded that the test substance is negative for the induction in micronuclei in vivo under the conditions of the test.