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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
The restrictions were that after exposure by inhalation for 6h per day for 5 days, sampling was carried out at 6 and 24 hours only; only 500 cells were scored to determine mitotic index.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994
Reference Type:
publication
Title:
No information
Author:
Vergnes et al.
Year:
2000
Bibliographic source:
Environ. Molec. Mutagen. 36, 13-21

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
yes
Remarks:
inhalation study, sampling times differ from recommended times
Principles of method if other than guideline:
Handbook of in vivo toxicity testing Arnold et al Academic press, New York NY.
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Octamethylcyclotetrasiloxane
EC Number:
209-136-7
EC Name:
Octamethylcyclotetrasiloxane
Cas Number:
556-67-2
Molecular formula:
C8H24O4Si4
IUPAC Name:
2,2,4,4,6,6,8,8-octamethyl-1,3,5,7,2,4,6,8-tetroxatetrasilocane

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague Dawley
- Age at study initiation: 5 weeks
- Weight at study initiation: 213-242 g (males); 135-163 g (females)
- Assigned to test groups randomly: yes
- Fasting period before study: no
- Housing: individually in stainless steel wire mesh cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 40-70 %
- Air changes (per hr): no information
- Photoperiod (hrs dark / hrs light): 12 hours

IN-LIFE DATES: From: 10 August 1993 To: 2 October 1993

Administration / exposure

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

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Wahmann inhalation chambers 101 x 101 x 60 cm, rectangular with pyramidal top and bottom; volume 900 l
- Source and rate of air: no information
- Method of conditioning air: filtered
- System of generating vapour: liquid D4 from a piston pump into heated glass evaporation chamber
- Temperature, humidity, pressure in air chamber:
- Air flow rate: approx 200 l/minute
- Air change rate: 13-14 air changes per hour
- Treatment of exhaust air: no information

TEST ATMOSPHERE
- Brief description of analytical method used: concentration in exposure chamber was monitored by flame ionization gas chromatography
- Samples taken from breathing zone: no information
Duration of treatment / exposure:
6 h/d
Frequency of treatment:
Once per day for 5 days
Post exposure period:
24 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 720 ppm (actual mean)
Basis:
analytical conc.
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
- Positive control substance: cyclophosphamide monohydrate
- Justification for choice of positive control(s): none given
- Route of administration: ip injection
- Doses / concentrations: 30 mg.kg bw

Examinations

Tissues and cell types examined:
Bone marrow
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: maximum achievable concentration of vapour.

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Animals were treated with Colchicine (4 mg/kg ip) 2-3 hours before sacrifice.

DETAILS OF SLIDE PREPARATION: Bone marrow cells were incubated for 20-30 minutes in hypotonic solution and then fixed with 3:1 methanol:acetic acid. Drops were air dried onto slides which were stained with Giesma. Additional slides were prepared as needed to ensure sufficient numbers of mitotic cells were available for analysis.

METHOD OF ANALYSIS: 5 animals per sex per treatment group per sampling time were selected for evaluation. Where possible, 100 cells per animal were scored for incidence and type of chromosome aberration.

OTHER: 500 cells per animal were scored to determine mitotic index.
Evaluation criteria:
A response is positive if there is a statistically significant exposure related increase in incidence of chromosomal aberrations.
Statistics:
Mann and Whitney's U-test.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Remarks:
in bone marrow
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
Positive control test substance cyclophosphamide induced markedly increased incidence of chromosomal aberrations in males and females.

Any other information on results incl. tables

There was a slight reduction in weight gain (males) or in body weight (females). There was no significant of dose-related increase in the incidence of chromosomal aberrations in rats exposed to D4 vapour. Table 1 Induction of chromosomal aberrations in rat bone marrow

Dose

0

700 ppm (6 hour)

700 ppm (24 hour)

Positive control

Number of animals

5

5

5

6

Cells counted

500

500

500

586

Total number of aberrant cells

2

5

6

99

Percentage aberrant cells

0.4

1.0

1.2

16.9

Applicant's summary and conclusion

Conclusions:
Octamethylcyclotetrasiloxane has been tested under GLP in a valid study which was conducted according to a protocol that is similar to OECD 475 and in compliance with GLP. There was no statistically significant increase in chromosome aberrations in rat bone marrow cells as a result of exposure to the test substance. It is concluded that Octamethylcyclotetrasiloxane is negative for clastogenicity (induction of chromosome aberrations) in rats under the conditions of the test.

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