Antimony pentachloride

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:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was generated according to valid testing guideline: OECD guideline 474

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

not specified

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Diantimony trioxide

EC Number:

215-175-0

EC Name:

Diantimony trioxide

Cas Number:

1309-64-4

Molecular formula:

Sb2O3

IUPAC Name:

dioxodistiboxane

Test material form:

not specified

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: male and female CD-1 mice supplied by Charles River Breeding Laboratories (Margate, UK)
- Age at study initiation: 5-11 weeks
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum



ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23°C
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12-hours light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

0.5% w/vhydroxypropylmethylcellulose in 0.1% w/v aqueous polysorbate 80.

Duration of treatment / exposure:

single oral gavage dose

Frequency of treatment:

once

Post exposure period:

Sampling times were 24 and 48 hours post dosing.

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
400 mg/kg
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
667 mg/kg
Basis:
nominal conc.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
1000 mg/kg
Basis:
nominal conc.

No. of animals per sex per dose:

5 male and 5 female

Control animals:

yes, concurrent vehicle

Positive control(s):

Cyclophosphamide was used as positive control.

Examinations

Tissues and cell types examined:

polychromatic erythrocytes

Details of tissue and slide preparation:

DETAILS OF SLIDE PREPARATION:
- Slides were scored blindly.

METHOD OF ANALYSIS:
Two thousand polychromatic erythrocytes were examined for micronuclei per animal.

Statistics:

The statistical analysis consisted of a one-sided Student´s t-test on transformed data.

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:

A significant decrease in the percent polychromatic erythrocytes was only seen in females at the 24 h sampling time in the single dose study.

Any other information on results incl. tables

Table 1: Assessment of antimony trioxide in the mouse bone marrow micronucleus assay: single dose, male

treatment	dose	males
.	.	mean incidence of MPE/1000 PE ± SD		mean % of polychromatic erythrocytes ± SD
.	.	24 hours	48 hours	24 hours	48 hours
Vehicle control	10 ml/kg	1.5 ± 0.6	0.2 ± 0.3	42.5 ± 8.9	37.6 ± 11.1
Cyclophosphamide	65 mg/kg	19.2 ± 5.2**		41.3 ± 5.2
Antimony trioxide	5000 mg/kg	0.8 ± 0.6	0.6 ± 0.7	41.9 ± 5.7	34.6 ± 13.9
PE: polychromatic erythrocytes; MPE: micronucleated polychromatic erythrocytes; SD: standard deviation. All means of MPE/1000 PE based on ten observations (two counts of 1000 PE per animal). All means of % PE based on five observations (one count of 1000 erythrocytes per animal). ** statistically significant increase or decrease over controls (p0.01 in Students t-test (one-sided) on transformed data).

Table 2: Assessment of antimony trioxide in the mouse bone marrow micronucleus assay: single dose, female

treatment	dose	females
.	.	mean incidence of MPE/1000 PE ± SD		mean % of polychromatic erythrocytes ± SD
.	..	24 hours	48 hours	24 hours	48 hours
Vehicle control	10 ml/kg	0.8 ± 0.5	0.6 ± 1.1	41.4 ± 8.8	44.2 ± 5.1
Cyclophosphamide	65 mg/kg	16.2 ± 2.8**		43.0 ± 6.6
Antimony trioxide	5000 mg/kg	1.4 ± 0.9	1.2 ± 0.9	26.7 ± 7.2**	39.9 ± 12.8
PE: polychromatic erythrocytes; MPE: micronucleated polychromatic erythrocytes; SD: standard deviation. All means of MPE/1000 PE based on ten observations (two counts of 1000 PE per animal). All means of % PE based on five observations (one count of 1000 erythrocytes per animal). ** statistically significant increase or decrease over controls (p0.01 in Students t-test (one-sided) on transformed data).

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
No statistically significant increase in the incidence of micronuclei was observed in the single or repeated dose study.