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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:
Jul 1991 - Nov 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with national standard methods with acceptable restrictions. Only 2 dose levels, only 4 animals in control group; no data about animal keeping

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991

Materials and methods

Test guideline
Qualifier:
no guideline followed
Deviations:
not applicable
Principles of method if other than guideline:
The test was conducted according to the two-phase experimental model as recommended by Przybojewska (1988).
GLP compliance:
no
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: fine crystalline solid matter
- Analytical purity: 89,4%

Test animals

Species:
mouse
Strain:
Balb/c
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: animal husbandry of Institute of the Nofer Institute of Occupational Medicine, Teresy, Poland
- Weight at study initiation: male - 24 g, female - 20 g


Administration / exposure

Vehicle:
- Vehicle(s)/solvent(s) used: distilled water
- Concentration of test material in vehicle: male - 64,32mg/10 ml; female - 56,40mg/10ml

Details on exposure:
The vehicle control, the test substance or Mitomycin C were administered in a volume of two times 0.5 ml as intraperitoneal injection.
Duration of treatment / exposure:
two treatments on the same day
Frequency of treatment:
two treatments on the same day
Post exposure period:
30 h, 48 h, 72 h
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
287 mg/kg
Basis:
nominal conc.
for female mice
Remarks:
Doses / Concentrations:
135 and 269 mg/kg
Basis:
nominal conc.
for male mice
No. of animals per sex per dose:
5
positive/negative control: 4
Control animals:
yes, concurrent vehicle
Positive control(s):
Mitomycin C;
- Doses / concentrations: 2,5 mg/kg

Examinations

Tissues and cell types examined:
Monochromatic and polychromatic erythrocytes
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: preliminary determination of LD50; chosen doses: 80%/ 40% of LD50

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): 30 h, 48 h and 72 h after dosing


METHOD OF ANALYSIS: 1000 polychromatic erythrocytes were evaluated for micronuclei. In addition, 1000 erythrocytes were counted to determine the ratio of polychromatic erythrocytes normochromatic erythrocytes.
Evaluation criteria:
Increase in the incidence of micronucleated polychromatic erythrocytes in any sex or at any time point (twice as much as in the negative control).
Percentage of polychromatic erythrocytes.
Statistics:
Mean value and standard deviation

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
not determined
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid

Any other information on results incl. tables

Table1a:

Genotoxicity Results of 2,4D acid of sodium salt in the micronucleus test for bone marrow on the mice BalbC strain, male

(LD50 i.p. for male mice: 336 mg/kg)

Tested substance

mg/kg

(% LD50)

No. of mice

 

No. of polychromatic erythrocytes

Percentage of polychromatic erythrocytes with micronuclei (± SD)

Ratio of polychromatic to normochromatic erythrocytes

 

 

 

30 h

48 h

72 h

30 h

48 h

72 h

Negative control1

5

5000

 

0,16 ±0,14

 

 

1,42

 

135 (40%)

5

5000

0,12 ±0,08

0,12 ±0,08

0,08 ±0,08

1,31

1,40

1,12

269 (80%)

10

10000

0,15 ±0,18

0,12 ±0,13

0,11 ±0,04

1,36

1,33

0,92*

Negative control1

4

4000

 

0,20 ±0,08

 

 

 

 

Positive control2

2,5

4

4000

3,47 ±0,20*

3,42 ±0,68*

0,80 ±0,45*

0,51*

0,21*

0,10*

Table1b: Genotoxicity Results of 2,4D acid of sodium salt in the micronucleus test for bone marrow on the mice BalbC strain, female (LD50i.p. for female mice: 353 mg/kg)

Tested substance

mg/kg

(% LD50)

No. of mice

 

No. of polychromatic erythrocytes

Percentage of polychromatic erythrocytes with micronuclei (± SD)

Ratio of polychromatic to normochromatic erythrocytes

 

 

 

30 h

48 h

72 h

30 h

48 h

72 h

Negative control1

5

5000

 

0,12 ±0,08

 

 

1,59

 

287

(80%)

5

5000

0,12 ±0,08

0,08 ±0,08

0,12 ±0,08

1,54

1,31*

0,96*

1– distilled water

2– Mitomycin C

*- statistically significant (p< 0,05)

 

Under the conditions tested, the test substance is not clastogenic in the mouse marrow micronucleus test.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative