Diethyl phosphonate

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:

other information

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Diethyl phosphonate

EC Number:

212-091-6

EC Name:

Diethyl phosphonate

Cas Number:

762-04-9

Molecular formula:

C4H11O3P

IUPAC Name:

diethyl phosphonate

Test material form:

other: clear liquid wotj weak odor

Details on test material:

content: 98.86 %

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation: 8-12 week
- Weight at study initiation:28-41 g
- Housing: males singly and females in groups of 3 mice
- Diet ad libitum
- Water ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22
- Humidity (%):40-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

corn oil

Details on exposure:

singel intraperitoneal injections fo 1500 mg/kg bw
Sacrifice 16 hours, 24 and 48 hours post injection

Duration of treatment / exposure:

once

Frequency of treatment:

once

Post exposure period:

up to 48 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
0 and 1500 mg/kg bw
Basis:

No. of animals per sex per dose:

5 males and 5 females

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamid

Examinations

Tissues and cell types examined:

polychromatic erythrocytes in somatic tissue, the bone marrow

Details of tissue and slide preparation:

Schmid's method was uded to produce smears and stained

Evaluation criteria:

Normally 1000 polychromatic erythrocytes were counted per animal,
an alteration of the ration poychromatic to normochromatic erythrocytes may show that the test compoA test actually reaches the target
a test was considered positive if , at any of the intervals there was a relevant and significant increase in the number of poychromatic erythrocytes showing micronuclei in comparison to the negative control

Statistics:

Wilcoxon*s non-parametric rank sum test. one-sided Chi--test, calculation of mean and standard deviation (1s)

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Executive summary:

Diethylphosphite was tested for clastogenic effects using the micronucleus test in accordance with OECD TG 474 and GLP. The known clastogen and cytostatic agend cyclophosphamide served as positive control.. The test animals received a single intraperitoneal injection of either diethyl phopsphite (1500 mg/kg bw) or cyclophosphamide, the femoral marrow of groups treated with diethyl phosphite was prepared 16, 24 and 48 hours after application.

The treated animals showed symptoms of toxicity after the administration , however, all animals survived until the end of the test.

There was an altered ratio between polychromatic and normochromatic erythrocytes.

No indications of a clastogenic effect of diethyl phopshphite were found. The positive control was functional..