(3-chloropropyl)dimethoxymethylsilane

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:

1995-11-07 to 1995-12-12

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP. The original study was considered reliability 1. Read-across to the registered substance is considered scientifically justified and is reliability 2.. The data are read across from (3-chloropropyl)diethoxymethylsilane (CAS 13501-76-3).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)

Version / remarks:

1992

Deviations:

yes

Remarks:

1600 PCE scored instead of 2000 (due to shift towards NCE)

GLP compliance:

yes (incl. QA statement)

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

(3-chloropropyl)diethoxymethylsilane

EC Number:

236-828-6

EC Name:

(3-chloropropyl)diethoxymethylsilane

Cas Number:

13501-76-3

Molecular formula:

C8H19ClO2Si

IUPAC Name:

3-chloropropyl(diethoxy)methylsilane

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: Harlan Winklemann, Borchen, Germany

- Age at study initiation: young adult

- Weight at study initiation: 35.8 ± 7.2 grams (male) / 31.8 ± 6.4 grams (female)

- Assigned to test groups randomly: yes, under following basis: colour code applied to the back of each animal; cage cards

- Fasting period before study: 16 - 18 hours prior to dosing procedure

- Housing: conventional, 5 animals/sex/Makrolon cage type III

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

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

- Acclimation period: ≥ 5 days

ENVIRONMENTAL CONDITIONS

- Temperature (°C): 22 ± 3 ˚c

- Humidity (%): 30 - 70 %

- Air changes (per hr): 15 changes per hour

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

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: corn oil

Details on exposure:

Route of exposure: intraperitoneal

Duration of treatment / exposure:

24 to 48 hours

Frequency of treatment:

Test compound and controls were administered once by intraperitoneal injection 10 ml/kg bw.

Post exposure period:

The positive control group was sacrificed 24 hours after administration of the test substance. The vehicle control and test substance groups were sacrificed 24 - 48 hours after administration of the test substance.

Doses / concentrations

Remarks:

Doses / Concentrations:
1600 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: intraperitoneal

- Doses / concentrations: 10 ml/kg bw of 0.9 % solution in physiological saline

Examinations

Tissues and cell types examined:

See table 2

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: pure erythrocyte suspension was used to prepare flat cells on glass by means of a Shandon Cytospin 3 (2 slides per animal). Slides were air dried and stained with May-Grundwald/Giemsa

METHOD OF ANALYSIS: A MIAMED image analyser equipped with the "Micronucleus Test V 4.00" software was used for fully automated slide scoring. Where possible, a total of approximately 2000 PCE (i.e. 10,000 PCE per treatment group) were analysed for micronuclei. The corresponding NCE were also scored for micronuclei. As an indicator for chemical-induced bone marrow toxicity, for each animal the PCE/NCE ratio was determined on the basis of 2000 PCE scored.

Evaluation criteria:

A test compound is considered an inducer of micronuclei in PCE, if at least one group of mice treated with the test compound reveals a statistically and biologically relevant increase in micronucleated PCE compared with the negative control.

Statistics:

Means and standard deviations of the following parameters were calculated for each treatment group:

-the number of PCE with micronuclei

-the number of NCE with micronuclei

-the PCE/NCE ratio.

"Statgraphics" statistical software was used to analyse data. Test compound groups were compared with negative control groups of the same sampling time. Heterogeneity between animals of the same dose group was tested for by calculating the heterogeneity χ2 for the differences between the proportions of micronuclei for each animal. Pearson's contingency χ2 with one degree of freedom including a Yates correcting factor used to make comparisons in homogenous groups. In the case of inhomogeneity between groups, after transformation of the data, a one-sided two-sample t-test is performed, and can also be used to compare the micronucleus frequencies of the positive control with the negative control groups for comparison of PCE/NCE ratios.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

PCE/NCE ratio reduced

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

See table 3

Any other information on results incl. tables

Table 3: Results of in vivo micronucleus test with Wacker BS 1701 

		Vehicle Control	Vehicle Control	Positive Control	1600 mg/kg bw	1600 mg/kg  bw
Number of cells evaluated		2000 approx.	2000 approx.	2000 approx.	2000 approx.	2000 approx.
Sampling time (h)		24	48	24	24	48
Number of erythro-cytes	normo­chromatic	NR	NR	NR	NR	NR
	poly­chromatic	2000 approx.	2000 approx.	2000 approx.	2000 approx.	2000 approx.
	polychromatic with micronuclei (%)	Male 0.16 % Female 0.13 %	Male 0.20 % Female 0.11 %	Male 4.1 % Female 2.2 %	Male 0.15 % Female 0.13 %	Male 0.2 % Female 0.18 %
Ratio of erythro­cytes	polychromatic / normochromatic (ratio)	Male 0.7 Female 0.81	Male 0.48 Female 1.38	Male 0.57 Female 0.83	Male 0.1 Female 0.14	Male 0.07 Female 0.09
	polychromatic with micro­nuclei / normochromatic	NR	NR	NR	NR	NR

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
(3-chloropropyl)diethoxymethylsilane was tested in an in vivo mouse micronucleus assay to EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test) and under GLP. No evidence for test substance mediated induction of micronuclei was observed. It is noted that the PCE / NCE ratio was reduced in the test substance-treated animals indicating the test substance had reached the target tissue. It is concluded that the test substance is not genotoxic under the conditions of the test. The result is a read across from (3-chloropropyl)diethoxymethylsilane (CAS 13501-76-3).