2-ethylhexyl 10-ethyl-4-[[2-[(2-ethylhexyl)oxy]-2-oxoethyl]thio]-7-oxo-8-oxa-3,5-dithia-4-phosphatetradecanoate 4-oxide

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

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPP 84-2

GLP compliance:

not specified

Type of assay:

mammalian erythrocyte micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexyl 10-ethyl-4-[[2-[(2-ethylhexyl)oxy]-2-oxoethyl]thio]-7-oxo-8-oxa-3,5-dithia-4-phosphatetradecanoate 4-oxide

EC Number:

280-479-2

EC Name:

2-ethylhexyl 10-ethyl-4-[[2-[(2-ethylhexyl)oxy]-2-oxoethyl]thio]-7-oxo-8-oxa-3,5-dithia-4-phosphatetradecanoate 4-oxide

Cas Number:

83547-95-9

Molecular formula:

C30H57O7PS3

IUPAC Name:

2-ethylhexyl 2-{[bis({2-[(2-ethylhexyl)oxy]-2-oxoethyl}sulfanyl)phosphoryl]sulfanyl}acetate

Test material form:

liquid

Details on test material:

- Other: Trade name D 16-051

Specific details on test material used for the study:

TEST MATERIAL (as stated in study report): TK 12 184

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor / Batch No. Mixt. 4/5/6

Test animals

Species:

hamster, Chinese

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: males - 23 - 32 g; females - 20 - 28 g
- Housing: individual
- Diet (e.g. ad libitum): Standard diet: NAFAG No.924
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23 deg C
- Humidity (%): 60-80%
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

distilled water

Details on exposure:

dosage volume of 20 mL/kg

Duration of treatment / exposure:

2 consecutive days

Frequency of treatment:

once per day

Post exposure period:

24 h

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

750 mg/kg bw/day (actual dose received)

Doses / concentrations 2

Dose / conc.:

1 500 mg/kg bw/day (actual dose received)

Doses / concentrations 3

Dose / conc.:

3 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

negative and positive controls: 3
treated groups: 6

Control animals:

yes, concurrent vehicle

Positive control(s):

cyclophosphamide - 128 mg/kg in 20 mL/kg of distilled water

Examinations

Tissues and cell types examined:

bone marrow

Details of tissue and slide preparation:

Bone marrow was harvested from the shafts of both femurs. In a siliconized pipette filled with approx. 0.5 µL rat serum the bone marrow was drawn up. In order to receive a homogeneous suspension the content of pipette was aspirated gently about three times. Small drops of the mixture were transferred on the end of a slide, spread out by pulling it behind a polished cover glass and the preparations were air-dried. Three hours later, the slides were stained in undiluted May-Grünwald solution for 2 min then in May-Grünwald solution/water 1/1 for 2 min and then in Giemsa's, 40% for 20 min. After being rinsed in methanol 55% for 5-8 sec and washed off twice in water, they were left immersed in water for approx, 2 min. After rinsing with distilled water and.air-drying, the slides were cleared in Xylol and mounted in Eukitt.

Evaluation criteria:

The slides of three female and three male animals each of the negative control group, the positive control group and of the groups treated with various doses of TK 12 184 were examined. 1000 bone marrow interphase cells each were scored per animal and the following anomalies were registered: a) Single Jolly bodies, b) fragments of nuclei in erythrocytes, c) micronuclei in erythroblasts, d) micronuclei in leucopoietic cells, e) polyploid cells.

Statistics:

The significance of difference was assessed by chi square test.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

The bone marrow smears from animals treated with various doses of TK 12 184 showed no significant difference from the control. The incidence.of bone marrow cells with anomalies of nuclei corresponds to the frequency observed in the control group.

By contrast, a "positive control" experiment with cyclophosphamide (128 mg/kg) yielded 13.8% cells with anomalies of nuclei. This is significantly different from the controls treated with the vehicle (distilled water) alone.

Applicant's summary and conclusion

Conclusions:

Under these test conditions no evidence of mutagenic effects was obtained in Chinese hamsters treated with TK 12 184 by oral gavage up to a limit dose of 3,000 mg/kg.