Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
other: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Reliability of original study is 1

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:
mammalian erythrocyte micronucleus test

Test material

Constituent 1
Chemical structure
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:
C16H35O2PS2.1/2Zn
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
- Fasting period before study:
- Housing: five per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 15
- Air changes (per hr):
- 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 hours
Frequency of treatment:
Once
Doses / concentrationsopen allclose all
Dose / conc.:
6 mg/kg bw/day
Dose / conc.:
12 mg/kg bw/day
Dose / conc.:
24 mg/kg bw/day
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide
- Route of administration: sterile water
- Doses / concentrations: 60 mg/kg

Examinations

Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION:
Range finding study performed to find the maximum tolerated dose

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):


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.

OTHER:
Evaluation criteria:
Statistically sifnificant dose-related increase in micronucleated PCE's and the detection of a statictically sifnificant postive 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
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
negative
Executive summary:

In the “Mammalian Erythrocyte Micronucleus Test”, according to GLP and OECD Guideline 474 mice (CD-1, male/female) were treated intraperitoneal with the test material (6, 12 and 24 mg/kg bw/day). No statistically significant increases in micronucleated polychromatic erythrocytes over the levels observed in the vehicle controls were observed in either sex, or at any harvest time point, or dose levels in mice.