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:
1991-05-07 to 1991-05-27
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted according to an OECD test guideline and under GLP, with acceptable restictions. The restrictions were that less detail was given than is usual in a standard micronucleus study, and there was no positive control. The result was obtained by valid read-across.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD 413
Deviations:
no
Principles of method if other than guideline:
Micronucleus data were gathered as part of a dose inhalation study, no positive control included.
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Source: not stated

- Age at study initiation: 5 - 7 weeks

- Weight at study initiation: 100 - 160 g

- Assigned to test groups randomly: yes, under following basis: using Xybion ASLECT program

- Housing: suspended, steel, wire mesh bottom cages.

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

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

ENVIRONMENTAL CONDITIONS

- Temperature (°F): 68 - 73 °F

- Humidity (%): 30 - 70 %

- Air changes (per hr): 12 - 15

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

Administration / exposure

Route of administration:
inhalation: vapour
Details on exposure:
TYPE OF INHALATION EXPOSURE: whole body

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure apparatus: 450 litre stainless steel whole body exposure chambers

- Source and rate of air: filtered room air

- Method of conditioning air: filtered with hepa and charcoal filters

- System of generating particulates/aerosols: test material introduced into chambers via special designed glass J-tubes, metered with FMI lab pumps. Glass beads and heating tape were used to help vapourize the test material.

- Air change rate: 12 - 15 air changes per hour
Duration of treatment / exposure:
Six hours/day
Frequency of treatment:
daily, 5 days a week for 2 weeks.
Post exposure period:
None
Doses / concentrations
Remarks:
Doses / Concentrations:
50 ppm
Basis:
nominal conc.
No. of animals per sex per dose:
5
Control animals:
yes, concurrent no treatment
Positive control(s):
none

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 serum, and a small drop was smeared on a slide and air dried overnight. The cells were fixed in methanol for 5 minutes.

METHOD OF ANALYSIS: microscopic examination. 2000 PCE scored for the incidence of polychromatic erythrocytes with micronuclei.

Statistics:
% Micronucleated PCE'S mean of 2000 per animal and mean ratio of PCE:NCE calculated with standard deviation. Data was analysed by a two-sided Welch trend test. If a significant overall trend was detected, then all follow up tests were one-sided and in the same direction as the overall trend. All tests were conducted at the 0.05 level of significance.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
reduction in PCE:NCE ratio relative to control
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
not examined

Any other information on results incl. tables

Table 3: Results of in vivo micronucleus test with Dow X2-2614

Exposure concentration (ppm)

0

50

Number of cells evaluated

2000

2000

Sampling time (d)

14 d

14 d

Number of erythro-cytes

normo­chromatic

NR

NR

poly­chromatic

2000

2000

% Micronucleated PCE’S (mean of 2000 per animal)

Male

 0.07

Female 0.15

Male

0.12

Female

0.05

Ratio of erythro­cytes

polychromatic / normochromatic

Male

1.8

Female

3.28

Male

1.12

Female

0.98

polychromatic with micro­nuclei / normochromatic

NR

NR

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Dimethoxymethylphenylsilane was tested in an in vivo micronucleus assay in rats (performed as part of a 14-day repeat dose inhalation toxicity study to OECD 413 and under GLP. It was not genotoxic under the conditions of the test.