Trichloro(2,4,4-trimethylpentyl)silane

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2000-11-27 to 2001-01-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP.

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)

Type of assay:

micronucleus assay

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

IUPAC Name:

triethoxy(2,4,4-trimethylpentyl)silane

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 (e.g. ad libitum): ad libitum

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

- Acclimation period: minimum of 5 days


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 19 - 25 ˚c

- Humidity (%): 49.5 - 61 %

- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: To: 15 January 2001

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 according to its relatively nontoxicity for the animals

- Lot/batch no. (if required): 36H0738

Details on exposure:

Route of exposure: Oral

Duration of treatment / exposure:

24 - 48 hours

Frequency of treatment:

The animals received the test item once orally.

Post exposure period:

Animals were sacrificed 24 - 48 h after treatment.

Doses / concentrations

Remarks:

Doses / Concentrations:
2000 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

five

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

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: limit dose

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): no further information

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-Grunwald (Merdk, 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 with Wacker BS 1701 

		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 erythro-cytes	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

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Triethoxy(2,4,4-trimethylpentyl)silane has been tested in a valid and reliable in vivo mouse micronucleus assay according to OECD 474 and under GLP. It was not genotoxic under the conditions of the test. The PCE / NCE ratio was only slightly affected in treated males, indicating that the test item had no or only slight toxic properties.