Registration Dossier

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

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:
ICR
Sex:
male/female

Administration / exposure

Route of administration:
intraperitoneal
Duration of treatment / exposure:
Single dose, with animals killed at 24 or 48 hours post-dosing
Doses / concentrations
Remarks:
Doses / Concentrations:
500, 1000, and 2000 mg/kg BW as a suspension in distilled water
Basis:

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
positive
Toxicity:
yes
Remarks:
Moderate to severe reductions of 22 to 59% in the ratio of polychromatic erythrocytes to total erythrocytes were observed in the test article-treated groups relative to the vehicle control animals. 
Vehicle controls validity:
valid
Negative controls validity:
not valid
Positive controls validity:
valid

Any other information on results incl. tables

One replacement group female died within 5 hours of dosing. 
All other mice survived to scheduled termination. Clinical
signs included lethargy and piloerection at 1000 and 2000
mg/kg.  

Moderate to severe reductions of 22 to 59% in the ratio of
polychromatic erythrocytes to total erythrocytes were
observed in the test article-treated groups relative to the
vehicle control animals.  Moderate reductions (22- 37%) were
observed in male and female dose groups 24 hours after
treatment with 500, 1000, and 2000 mg/kg and severe
reductions (45-59% were observed in male and female mice 48
hours post-treatment.  A reduction greater than 90% in the
number of polychromatic erythrocytes was evident 48 hours
post-treatment in 2 males at 2000 mg/kg.  The number of PCEs
was not enumerated in these cases.  A significant increase
in micronucleated PCEs was observed in male and female mice
24 hours post-dosing in the 500, 1000, and 2000 mg/kg dose
groups and at 48 hours post-dosing in the 2000 mg/kg dose
group.  The positive control substance also induced a
significant increase in micronucleated PCEs.

Summary of Bone Marrow Micronucleus Study - 24 hrs

Treatment

Sex

No of mice

PCE/total erythrocytes (mean +/- SD)

Change from control (%)

Micronucleated PCEs per 1000 PCEs (mean +/- SD)

Erythrocytes Number per PCEs scored

Water(1

M

5

0.54+/- 0.01

--

0.3+/-0.27

3/10000

Water(1)

F

5

0.55+/- 0.03

--

0.3+/-0.27

3/10000

TMSPGE      

500 mg/kg

M

5

0.40+/-0.08

-26

3.2+/-1.04

*32/10000

500 mg/kg

F

5

0.42+/-0.01

-24 

3.9+/-3.31

*39/10000

1000 mg/kg

M

5

0.35+/-0.08

-35 

8.8+/-1.82

*88/10000

1000 mg/kg

F

5

0.43+/-0.10

-22 

14.7+/-5.51

*147/10000

2000 mg/kg

M

5

0.34+/-0.05

-37

24.3+/-7.03

*243/10000

2000 mg/kg

F

5

0.38+/-0.07

-31

24.1+/-8.39

*241/10000

CP(2)

M

5

0.35+/-0.08

-35

25.7+/-6.62

*257/10000

CP(2)

F

5

0.38+/-0.09

-31

24.3+/-5.09

*243/10000

                         
1 = 20 ml/kg
2 = 50 mg/kg
* = p<0.05 (Kastenbaum-Bowman Tables)

Treatment

Sex

No of mice

PCE/total erythrocytes (mean +/- SD)

Change from control (%)

Micronucleated PCEs per 1000 PCEs (mean +/- SD)

Erythrocytes Number per PCEs scored

Water(1

M

5

0.51+/-0.05

--

0.1+/-0.22

1/10000

Water(1)

F

5

0.53+/-0.05

--

0.3+/-0.27

3/10000

TMSPGE      

2000 mg/kg

M

5

0.21+/-0.15 

-59

3.3+/-1.61(3)

*20/60003

2000 mg/kg

F

5

0.29+/-0.12 

-45

6.1+/-6.64

*61/10000


(2) = 50 mg/kg
(3) = due to severe reduction in number of PCEs, MPCE out of
2000 PCE was not enumerated for two male mice. Values
determined using three mice.
* = p<0.05 (Kastenbaum-Bowman Tables)

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): positive
The test substance, 3-glycidoxypropyltrimethoxysilane, induced chromosome damage in the bone marrow cells of mice following i.p. administration of the test substance at all three dose levels tested.