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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
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Methacrylonitrile
EC Number:
204-817-5
EC Name:
Methacrylonitrile
Cas Number:
126-98-7
Molecular formula:
C4H5N
IUPAC Name:
methacrylonitrile
Details on test material:
- Name of test material (as cited in study report): Methacrylonitrile
- Substance type: organic aliphatic nitrile
- Physical state: liquid, colorless
- Analytical purity: 99.9%
- Lot/batch No.: JY00427ET
- Supplier: Aldrich Chemical Company, Milwaukee, WI
- Stability under test conditions: no significant decomposition was observed by gas chromatographical analysis during the study
- Storage condition of test material: protected from light at 5 degrees Centigrade

Test animals

Species:
other: rat and mice
Strain:
not specified
Sex:
male
Details on test animals or test system and environmental conditions:
no data

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
Corn oil
Details on exposure:
No data
Duration of treatment / exposure:
96h
Frequency of treatment:
3 injections at 24h intervals
Post exposure period:
24h after the last injection
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 12, 25, 50, 100, and 200 mg/kg bw
Basis:
nominal conc.
for rats
Remarks:
Doses / Concentrations:
0, 6.25, 12.5, and 25 mg/kg bw
Basis:
nominal conc.
for mice
No. of animals per sex per dose:
Five animals per dose group
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide

Examinations

Tissues and cell types examined:
Polychromatic erythrocytes (PCEs) derived from bone marrow
Details of tissue and slide preparation:
The animals were killed 24 hours after the third injection, and slides were prepared from bone marrow cells obtained from the femurs. Air-dried smears were fixed and stained; 2,000 polychromatic erythrocytes (PCEs) were scored for the frequency of micronucleated cells in each of up to five animals per dose group.
Evaluation criteria:
In the used micronucleus test, an individual trial is considered positive if the trend test P value is less than or equal to 0.025 or if the P value for any single dose group is less than or equal to 0.025 divided by the number of dose groups.
Statistics:
The frequency of micronucleated cells among PCEs was analyzed by a statistical software package that tested for increasing trend over dose groups with a one-tailed Cochran-Armitage trend test, followed by pairwise comparisons between each dosed group and the control group (ILS, 1990).

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Remarks:
rats and mice
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
In a male rat bone marrow micronucleus test, an initial trial showed a significant induction of micronuclei in the 25 mg/kg group; however, a second trial showed no induction of micronuclei in bone marrow polychromatic erythrocytes, and the test was determined to be negative overall . Also, no increase in the frequency of micronucleated polychromatic erythrocytes was observed in the bone marrow of male mice treated with 6.25 to 25 mg/kg methacrylonitrile.

Any other information on results incl. tables

Table 1: Induction of Micronuclei in Bone Marrow Polychromatic Erythrocytes of Male Rats Treated with Methacrylonitrile by Intraperitoneal Injection

Compound

Dose [mg/kg bw]

Number of rats scored

Micronucleolated PCEs/1000 PCEsb

P valuec

Trial 1

Corn oild

 

4

0.25±0.14

 

Cyclophosphamidee

25

4

6.00±0.98

0.0000

Methacrylonitrile

25

5

1.40±0.37

0.0050

 

50

3

0.83±0.44

0.0633

 

100

2f

0.50±0.50

 

 

200

 

Lethal

 

 

 

 

 

P=0.086g

Trial 2

Corn oild

 

5

1.80±0.46

 

Cyclophosphamidee

25

3

4.00±0.29

0.0042

Methacrylonitrile

12

5

1.10±0.37

0.9033

 

25

5

1.60±0.29

0.6343

 

50

 

Lethal

 

 

 

 

 

P=0.643g

PCE=polychromatic erythrocyte

bMean ± standard error

cPairwise comparison with the solvent control

dSolvent control

ePositive control

fOmitted from statistical analysis; invalid data point due to poor survivability

gSignificance of micronucleated PCEs/1,000 PCEs tested by the one-tailed trend test, significant at P0.025

 

Table 2: Induction of Micronuclei in Bone Marrow Polychromatic Erythrocytes of Male Mice Treated with Methacrylonitrile by Intraperitoneal Injection

Compound

Dose [mg/kg bw]

Number of rats scored

Micronucleolated PCEs/1000 PCEsb

P value

Trial 1

Corn oilc

 

5

1.00±0.16

 

Cyclophosphamided

25

5

3.30±0.60

 

Methacrylonitrile

6.25

5

1.60±0.62

 

 

12.5

5

1.60±1.23

 

 

25

3

1.17±1.17

 

 

 

 

 

P=0.450e

PCE=polychromatic erythrocyte

bMean ± standard error

cSolvent control

dPositive control

eSignificance of micronucleated PCEs/1,000 PCEs tested by a one-tailed trend test, significant at P0.025

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Using an in vivo micronucleus test in male rats and mice, no evidence of in vivo genotoxicity of methacrylonitrile could be shown.