Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
December 3, 1991 to June 9, 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
mammalian bone marrow chromosome aberration test

Test material

Test material form:
solid

Test animals

Species:
mouse
Strain:
ICR
Sex:
male/female

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
Corn oil
Details on exposure:
Initial micronucleus assay: 5/sex/time point/group for CP (30 mg/kg bw), 0, 1250, 2500, or 5000 mg/kg groups; Confirmatory micronucleus assay: 6/sex/group for CP (30 mg/kg bw), 0, 2500, or 5000 mg/kg bw groups
Control animals:
yes

Results and discussion

Test results
Key result
Sex:
not specified
Genotoxicity:
positive

Any other information on results incl. tables

Evaluations: No mortality or clinical signs were observed in either male or female mice in the micronucleus assay. Bone marrow cells, collected 24, 48, and 72 hours after treatment, were examined microscopically for micronucleated polychromatic erythrocytes. No reduction in the ratio of polychromatic erythrocytes to total erythrocytes was observed in the male or female treatment groups suggesting that the test article did not induce bone marrow toxicity. No significant increase in micronucleated polychromatic erythrocytes was observed at 24, 48 or 72 hours after dose administration in the male mice. However, a significant increase in micronuclcated polychromatic erythrocytes was observed at dose levels of 2500 and 5000 mg/kg in female mice, only at the 48 hour sampling time.

In order to confirm the statistical increase of micronucleated polychromatic erythrocytes observed in females at dose levels of 2500 and 5000 mg/kg bw at the 48 hour bone marrow collection time, a confirmatory micronucleus assay was initiated. Male and female ICR mice were exposed to 2500 or 5000 mg/kg bw of antimony dipentyldithiocarbamate which was administered in a total volume of 20 ml/kg as a single IP injection. No mortality or clinical signs were observed in either male or female mice in the confirmatory micronucleus assay. Bone marrow cells, collected 48 hours after dose administration, were examined microscopically for rnicronucleated polychromatic erythrocytes. No reduction in the ratio of polychromatic erythrocytes to total erythrocytes was observed in the male or female treatment groups suggesting that the test article did not induce bone marrow toxicity. No significant increase in micronucleated polychromatic erythrocytes was observed in the male mice; however, a significant increase in micrornucleated polychromatic erythrocytes was observed at dose levels of 2500 and 5000 mg/kg bw in female mice.

The results of the initial and confirmatory assay indicate that under the conditions described in this study, antimony dipentyldithiocarbamatedid induce a reproducible, significant treatment-related increase in the incidence of micronucleated polychromatic erythrocytes in the bone marrow of female mice at the 48 hour sampling time. Considerable inter-animal variability was observed in the dose groups that were significantly elevated above the vehicle control group. Antimony dipentyldithiocarbamate was concluded to be weakly positive in the mouse micronucleus assay.

Applicant's summary and conclusion

Conclusions:
Under the conditions of the study, Antimony dipentyldithiocarbamate was concluded to be weakly positive in the mouse micronucleus assay.
Executive summary:

A study has been conducted on the Read-Across substance Antimony Dipentyldithiocarbamate. The study conducted was a mouse micronucleus test performed under GLP conditions. Although no guidelines were stated within the study, the methodology is similar or equivalent to the standardized OECD 474; hence the study has been assigned a Klimisch score of 2.

The study was performed on ICR mice, utilizing corn oil as the vehicle. In the pilot study, antimony dipentyldithiocarbamate was administered by a single IP injection to 2 males/group at 1, 10, 100, or 1000 mg/kg bw and to 5 animals/sex at 5000 mg/kg bw in corn oil with dosing volume of 20 ml/kg bw. In the absence of mortality in the pilot study, the dose levels for the micronucleus assay were set at 1250, 2500 or 5000 mg/kg bw.

Dosing solution of antimony dipentyldithiocarbamate in corn oil (250 mg/ml) was analyzed and confirmed the concentration using atomic absorption.

No mortality or clinical signs were observed in either male or female mice in the micronucleus assay. Bone marrow cells, collected 24, 48, and 72 hours after treatment, were examined microscopically for micronucleated polychromatic erythrocytes. No reduction in the ratio of polychromatic erythrocytes to total erythrocytes was observed in the male or female treatment groups suggesting that the test article did not induce bone marrow toxicity. No significant increase in micronucleated polychromatic erythrocytes was observed at 24, 48 or 72 hours after dose administration in the male mice. However, a significant increase in micronuclcated polychromatic erythrocytes was observed at dose levels of 2500 and 5000 mg/kg in female mice, only at the 48 hour sampling time.

In order to confirm the statistical increase of micronucleated polychromatic erythrocytes observed in females at dose levels of 2500 and 5000 mg/kg bw at the 48 hour bone marrow collection time, a confirmatory micronucleus assay was initiated. Male and female ICR mice were exposed to 2500 or 5000 mg/kg bw of antimony dipentyldithiocarbamate which was administered in a total volume of 20 ml/kg as a single IP injection. No mortality or clinical signs were observed in either male or female mice in the confirmatory micronucleus assay. Bone marrow cells, collected 48 hours after dose administration, were examined microscopically for rnicronucleated polychromatic erythrocytes. No reduction in the ratio of polychromatic erythrocytes to total erythrocytes was observed in the male or female treatment groups suggesting that the test article did not induce bone marrow toxicity. No significant increase in micronucleated polychromatic erythrocytes was observed in the male mice; however, a significant increase in micrornucleated polychromatic erythrocytes was observed at dose levels of 2500 and 5000 mg/kg bw in female mice.

The results of the initial and confirmatory assay indicate that under the conditions described in this study, antimony dipentyldithiocarbamatedid induce a reproducible, significant treatment-related increase in the incidence of micronucleated polychromatic erythrocytes in the bone marrow of female mice at the 48 hour sampling time. Considerable inter-animal variability was observed in the dose groups that were significantly elevated above the vehicle control group. Antimony dipentyldithiocarbamate was concluded to be weakly positive in the mouse micronucleus assay.