Sodium 2,4-dichlorophenoxyacetate

Genetic toxicity: in vivo

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

Test material information

Constituent 1

Reference substance name:

Sodium 2,4-dichlorophenoxyacetate

EC Number:

220-290-4

EC Name:

Sodium 2,4-dichlorophenoxyacetate

Cas Number:

2702-72-9

Molecular formula:

C8H6Cl2O3.Na

IUPAC Name:

sodium 2-(2,4-dichlorophenoxy)acetate

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 or test system 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 / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
287 mg/kg
Basis:
nominal conc.
for female mice

Doses / concentrations 2

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 control^1	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 control^1	4	4000		0,20 ±0,08
Positive control^2 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 control^1	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