Registration Dossier

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:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Similar to guideline with deficiencies in data reporting

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2'-oxybis[5,5-dimethyl-1,3,2-dioxaphosphorinane] 2,2'-disulphide
EC Number:
223-829-1
EC Name:
2,2'-oxybis[5,5-dimethyl-1,3,2-dioxaphosphorinane] 2,2'-disulphide
Cas Number:
4090-51-1
Molecular formula:
C10H20O5P2S2
IUPAC Name:
2-[(5,5-dimethyl-2-sulfanylidene-1,3,2λ⁵-dioxaphosphinan-2-yl)oxy]-5,5-dimethyl-1,3,2λ⁵-dioxaphosphinane-2-thione

Test animals

Species:
mouse
Strain:
other: CFLP
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Anglia Laboratory Animals, Huntingdon, UK
- Weight at study initiation: 19-23 g
- Assigned to test groups randomly: yes
- Housing: in groups of 5
- Diet (ad libitum): Grain Harvester Anglia Laboratory Animal diet
- Water (ad libitum): tap water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 50 +/- 5

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: corn oil
- Concentration of test material in vehicle: 125-500 mg/mL
- Amount of vehicle (if gavage or dermal): 0.1 mL
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
with Silverstone high speed mixer
Duration of treatment / exposure:
24 h between first and second application
Frequency of treatment:
twice
Post exposure period:
6 h after second application
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 2500, 5000, 10000 mg/kg
Basis:
nominal conc.
divided in two doses, separated by a 24 h interval
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
mitomycin C
- Doses / concentrations: 2 x 7 mg/kg

Examinations

Tissues and cell types examined:
2000 polychromatic erythrocytes from bone marrow smears per animal
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION:
based on a preliminary toxicity test

DETAILS OF SLIDE PREPARATION:
fixed in methanol, defatted in xylene and stained by Giemsa

METHOD OF ANALYSIS:
optical examination
Evaluation criteria:
not stated in detail
Statistics:
not stated

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
- Dose range: 0-10000 mg/kg (divided in 2 doses, separated by an interval of 24 h)
- Clinical signs of toxicity in test animals: no toxic effects, no mortality

Any other information on results incl. tables

Historical control values from the laboratory were reported for comparison

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Under the conditions of this study the test substance did not induce micronuclei in mice in the bone marrow.
Executive summary:

CFLP mice (5 per sex and dose) were gavaged with 0, 2500, 5000 and 10000 mg/kg (divided in 2 applications) of the test item. 6 h after the second dose, polychromatic erythrocytes from bone marrow were analysed for the induction of micronuclei. Under the conditions of this study the test substance did not induce micronuclei. In addition, no other toxic effects were oberved.  

An appropriate positive control showed a mutagenic response, thus confirming the validity of this study.