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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar 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:
Swiss Webster
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: not stated
- Weight at study initiation: 15-5 g (female); 20-30 g (male)
- Assigned to test groups randomly: yes
- Fasting period before study: no
- Housing: shoe-vox type plastic cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 to 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled but not specified in report
- Humidity (%): controlled but not specified in report
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12:12

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
Corn oil; all solutions made just before dosing.
Substance reacted slowly with water.
Duration of treatment / exposure:
30, 48 and 72 hour
Frequency of treatment:
One treatment
Post exposure period:
Samples taken 30,48 and 72 hours after treatment
Doses / concentrations
Remarks:
Doses / Concentrations:
2500, 4000 and 5000 mg/kg bw
Basis:

No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
yes, concurrent vehicle
Positive control(s):
- Positive control substance: triethylenemelamine
- Route of administration: ip injection
- Doses / concentrations: 0.3 and 0.5 mg/kg bw

Examinations

Tissues and cell types examined:
Peripheral blood; 1000 Polychromatic erythrocytes (PCE) examined for micronuclei; PCE/NCE (normochromatic erythrocyte) ratio calculated for approximately 1000 total cells
Evaluation criteria:
Results were considered positive under the following conditions:
-at least one statistically significant increase above the control was obtained and there was a statistically significant indication of a dose-related effect of treatment;
- at least two dose level from the same sample period produced micronucleus frequencies which were significantly above the control values;
- at least two dose level from the same sample period produced micronucleus frequencies which were significantly above the control values and there was an indication of a significant dose-related increase in at least one of the sample intervals

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
25% reduction in proportion of PCEs at MTD 72h post dose
Vehicle controls valid:
yes
Negative controls valid:
not applicable
Positive controls valid:
yes
Remarks on result:
other: No mutagenic potential

Any other information on results incl. tables

Table 1 Results of micronucleus assay

Dose mg/kg

Collection interval (hours)

%Micronucleated PCE’s1

Mean ± S.D

Ratio PCE : NCE2

Mean ± S.D

 

 

Males

Females

Males

Females

2500

30

0.46± 0.35

0.34± 0.34

41.4± 11.8

46.4± 20.8

48

0.50± 0.49

0.20± 0.29

38.6± 14.9

34.5± 9.8

72

0.18± 0.05

0.28± 0.38

21.4±4.4

27.2± 2.9

4000

30

0.52± 0.27

0.20± 0.10

43.6± 11.3

53.2± 16.4

48

0.42± 0.33

0.26± 0.23

37.2± 4.8

44.6± 14.7

72

0.14± 0.11

0.18± 0.18

23.2± 6.4

24.6± 8.7

5000

30

0.24± 0.11

0.38± 0.15

43.6± 10.1

40.8± 12.2

48

0.34± 0.15

0.22± 0.05

32.2± 11.1

38.3± 6.2

72

0.26± 0.17

0.18± 0.18

19.8± 5.4

21.0± 12.3

Vehicle (corn oil)

30

0.30±0.12

0.36±0.11

44.6± 12.4

47.6± 11.3

48

0.34± 0.18

0.14± 0.11

42.4± 10.9

44.2± 11.4

72

0.24± 0.17

0.04± 0.06

29.4±6.7

32.0± 8.5

Positive control 0.3 mg/kg

30

2.92± 0.9

2.84± 1.00

34.4± 10.0

29.8± 8.2

48

NE

NE

NE

NE

 

NE

NE

NE

NE

1 Polychromatic erythrocytes

2 Normochromatic erythrocytes

Applicant's summary and conclusion

Conclusions:
3-Trimethoxysilylpropyl methacrylate has been tested under GLP in a reliable, valid mouse micronucleus assay according to a protocol that is similar to OECD TG 474. The test substance did not produce treatment-related or statistically significant increases in the incidence of micronuclei in the peripheral blood polychromatic erythrocytes when administered by intraperitoneal injection up to limit concentrations. A decrease in the PCE/NCE ratio at 72 hours was considered to be evidence that the test substance had reached the target tissue. Positive and vehicle controls produced appropriate responses. It is concluded that the test substance is negative for the induction of micronuclei under the conditions of the test.