Phosphorodithioic acid, O,O-di-dodecyl-esters, zinc salts, neutral and basic

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

other: cytogenicity / erythrocyte micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate)

EC Number:

224-235-5

EC Name:

Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate)

Cas Number:

4259-15-8

Molecular formula:

Too complex

IUPAC Name:

1-Hexanol, 2-ethyl-, O,O-diester with phosphorodithioic acid, zinc salt

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8 weeks and 2 days
- Weight at study initiation: 29.8-37.8 g (male) and 23.3-28.8 g (female)
- Assigned to test groups randomly: yes
- Housing: five per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 15
- Photoperiod (hrs dark / hrs light): 12 hours

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: Peanut oil
- Amount of vehicle (if gavage or dermal): 10 mL

Duration of treatment / exposure:

24, 48, and 72 h

Frequency of treatment:

Once

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

6 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

12 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

24 mg/kg bw/day (nominal)

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide
- Vehicle: sterile water
- Doses / concentrations: 60 mg/kg bw

Examinations

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION:
Range finding study performed to find the maximum tolerated dose

DETAILS OF SLIDE PREPARATION:
Slides fixed with methanol and stained in May-Grunwald solution followed by Giemsa.

METHOD OF ANALYSIS:
Scored for micronuclei and the polychromatic erythrocyte (PCE) to normochromatic erythrocyte (NCE) cell ration.

Evaluation criteria:

Statistically sifnificant dose-related increase in micronucleated PCE's and the detection of a statistically sifnificant positive response for at least one dose level.

Statistics:

The frequency of micronucleated polychromatic erythrocytes between treated groups and vehicle controls were compared. Tests included Cochran-Armitage test for trend, a one-way analysis of variance and Dunnett’s procedure.

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study, the frequency of micronucleated polychromatic erythrocytes was not increased in treated mice when compared with the control group.