Registration Dossier

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:
2002-09-27 to 2002-11-28
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP. It is considered that read-across to the registered substance is scientifically justified.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2003

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Italy
- Age at study initiation: no information
- Weight at study initiation: 20.8-27.2 g
- Assigned to test groups randomly: [no/yes, under following basis: ]
- Fasting period before study: no
- Housing: 5 animals per cage, polycarbonate with stainless steel mesh lid and floor
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 55
- Air changes (per hr): no information
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: From: not given To: 2002-10-04

Administration / exposure

Route of administration:
oral: gavage
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: prepared immediately before use in corn oil
Frequency of treatment:
Single treatment
Post exposure period:
Samples taken at 24 or 48 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
0 (corn oil), 500, 1000, and 2000 mg/kg
Basis:
other: expressed i terms of material as received. Solutions prepared on w/v basis without correction for displacement
No. of animals per sex per dose:
5/sex/dose
Control animals:
yes, concurrent vehicle
Positive control(s):
- mitomycin C
- Justification for choice of positive control(s): none given, standard control
- Route of administration: ip injection
- Doses / concentrations: 3.0 mg/lg body weight

Examinations

Tissues and cell types examined:
Bone marrow
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: preliminary toxicity assay

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

DETAILS OF SLIDE PREPARATION: air dried and stained with May-Gruenwald and Giesma

METHOD OF ANALYSIS: 200 PCEs per animal examined for presence of micronuclei at high power (x100, oil immersion)

OTHER:
Evaluation criteria:
A test item is considered positive if it induces a statistically significant increase, exceeding the historical range of negative control values, in the incidence of micronucleated PCEs (p<0.05) in pooled data for both sexes or for either sex considered separately.
Statistics:
Original observations of polychromatic cells from control and treated groups were compared using a modified Chi-squared evaluation

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative

Any other information on results incl. tables

Animals from the high dose treatment group showed reduced activity,  ataxia and hunched posture.  Animals from the intermediate dose treatment  group showed hunched posture and an animal died after treatment.   Clinical signs and mortality were observed and provided evidence of  bioavailability of the test substance and adequate exposure time.  Following treatment with the test substance, no statistically significant  increase in the incidence of micronucleated PCE's over the control value  was observed at any dose-level, at any sampling time.  Following  treatment with the positive control Mitomycin-C, statistically  significant increases in the incidence of micronucleated PCEs over the  control values were observed, indicating the correct functioning of the  test system.  

The test was conducted at the limit dose of 2000 mg/kg bw at which signs  of toxicity were seen (mortality, reduced activity, ataxia and hunched  posture) indicating bioavailability of the test substance.  When tested  at the limit dose with no or minimum signs of toxicity and with the  positive and negative controls responding appropriately, the test is  considered valid.


The ratio of mature to immature to immature erythrocytes and the  proportion of immature erythrocytes to among total erythrocytes were  analyzed to evaluate the bone marrow cell toxicity. No inhibitory effect  on erythropoetic cell division was observed for either sex at any  sampling time. 

The report contains the values for PCE and NCE separately, as well as  ratios of NCE/PCE and PCE/(NCE+PCE). P/N ratios were not calculated in  the report.

Dose

PCE

NCE

NCE/PCE ratio

PCE/(NCE+PCE)

0

20527

25105

1.22

0.45

500

20601

22891

1.11

0.47

1000

18525

21590

1.17

0.44

2000

20504

26333

1.28

0.44

Positive control

20847

35393

1.69

0.37


Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Trimethoxy(methyl)silane has been tested in a valid study according to OECD 474 and under GLP. No increase in the indicence of micronucleated PCE was observed resulting from exposure to the test substance by oral gavage up to limit concentrations. It is concluded that the test substance is negative for the induction of micronuclei under the conditions of the test.