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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
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given: scientifically acceptable study summary including result tables; the test protocol can be viewed online.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1989

Materials and methods

Principles of method if other than guideline:
According to the NTP standard protocols
GLP compliance:
no
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Allyl glycidyl ether

Test animals

Species:
mouse
Strain:
not specified
Sex:
male

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: physiol. saline
Frequency of treatment:
3, administered at 24 hr intervals
Doses / concentrations
Remarks:
Doses / Concentrations:
50, 100 and 200 mg/kg bw
Basis:

No. of animals per sex per dose:
3-5 (3 males were used in trial 1 at dose level of 200 mg/kg bw; in the 2nd trial, 5, 4 and 5 mice were used at dose levels of 50, 100 and 200 mg/kg bw, respectively)
Control animals:
yes, concurrent vehicle
Positive control(s):
mitomycin C
- Doses / concentrations: 0.2 mg/kg bw

Examinations

Tissues and cell types examined:
bone marrow
Details of tissue and slide preparation:
TREATMENT AND SAMPLING TIMES: harvesting of the bone marrow done at 24 hours after the last dosing.

DETAILS OF SLIDE PREPARATION: The animals are euthanized by CO2 inhalation and the femurs are removed. The bone marrow is flushed from the femurs and spread onto slides. The slides are air-dried, fixed, and stained with a fluorescent DNA-specific stain that easily illuminates any micronuclei that may be present. Typically, 2000 polychromatic erythrocytes (PCEs, reticulocytes; immature erythrocytes) are scored per animal for frequency of micronucleated cells in each of 3-5 animals per dose group.

Results and discussion

Test results
Sex:
male
Genotoxicity:
positive
Toxicity:
not specified
Vehicle controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

     Trial 1:

 

Dose (mg/kg)

Number of Animals Scored

Mean MN-PCE/1000 PCE ± SEM

Pairwise P

Phosphate Buffered Saline

 0         

3

1.67 ± 1.20

 

Allyl glycidyl ether

200         

3

14.67 ± 2.03

< 0.0001

Mitomycin-C

 0.2       

2

10.50 ± 3.50

*

    * Insufficient animals scored to calculate p-value.

   

    Trial 2:

 

Dose (mg/kg)

Number of Animals Scored

Mean MN-PCE/1000 PCE ± SEM

Pairwise P

Phosphate Buffered Saline

0

3

1.67 ± 1.20

 

 

Allyl glycidyl ether

50

5

4.40 ± 0.43

0.001

100

4

5.88 ± 0.90

< 0.0001

200

5

20.00 ± 2.01

< 0.0001

Mitomycin-C

0.2

5

6.50 ± 0.42

< 0.0001

 

Applicant's summary and conclusion