Dipotassium bis[μ-[tartrato(4-)-O1,O2:O3,O4]]diantimonate(2-) , stereoisomer

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Type of information:

other: Bibliographic source

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

in accordance with the recommendations of the Ad Hoc Committee of Mutagenicity Testing [Nichols et al, 19721

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: The experimental procedure was conducted in accordance with the recommendations of the Ad Hoc Committee of Mutagenicity Testing

Principles of method if other than guideline:

In order to study the chromosomal aberrations induced by tartar emetic , male rats (Rattus norvegicus) 8-15 weeks old were used. The experimental procedure was conducted in accordance with the recommendations of the Ad Hoc Committee of Mutagenicity Testing [Nichols et al, 19721]. Both drugs were administered intraperitoneally at three different doses: the clinical (usage) dose, an intermediate dose, and the maximum tolerated dose (MTD), which is considered to be equal to the LDs that was determined experimentally [El Nahas, 19791. These doses are 2, 8.4, 14.8 mg/kg for tartar emetic.
Each dose was studied both acutely (6,24, and 48 hours after a single injection) and subacutely where the drug was given for 5 consecutive days and the rats were killed 6 hours later. Five rats were sacrificed in each treatment group, and four untreated rats served as control for each dose.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

Cas Number:

28300-74-5

Molecular formula:

C8H4K2O12Sb2 ∙ 3H2O

Details on test material:

Trihydrate salt.

Specific details on test material used for the study:

form of the substance (anhydrous or trihydrated) not specified.

Test animals

Species:

rat

Strain:

other: Rattus norvegicus

Sex:

male

Administration / exposure

Route of administration:

intraperitoneal

Details on exposure:

the substance was administered intraperitoneally at three different doses: the clinical (usage) dose, an intermediate dose, and the maximum tolerated dose (MTD), which is considered to be equal to the LD5. These doses are 2, 8.4, 14.8 mg/kg

Duration of treatment / exposure:

Each dose was studied both acutely (6,24, and 48 hours after a single injection) and subacutely

Frequency of treatment:

the drug was given for 5 consecutive days and the rats were killed 6 hours later.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

2 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

8.4 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

14.8 mg/kg bw/day (nominal)

No. of animals per sex per dose:

Five rats were sacrificed in each treatment group, and four untreated rats served as control for each dose.

Control animals:

yes

Applicant's summary and conclusion

Conclusions:

Tartar emetic induced chromosomal aberrations,namely chromatid gaps, chromatid breaks, and centric fusion.
Tartar Emetic significantly increased (relative to control) the number of metaphases with chromosomal aberrations after 6,24, and 48 hours of both acute
and subacute treatments at three different doses. There were no significant differences in chromosomal aberrations after 6, 24,and 48 hours of the acute treatment at all doses tested. An exceptional case was recorded 6 hours after the MTD (14.8 mg/kg); here the number of cells with aberrations was significantly higher than its 24-hour and 48-hour counterparts.