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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

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

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

Justification for type of information:

Common functional groups

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

basic toxicokinetics, other

Type of information:

other:

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Objective of study:

toxicokinetics

GLP compliance:

not specified

Radiolabelling:

yes

Details on absorption:

Antimony compounds may be absorbed by inhalation and ingestion.

Details on distribution in tissues:

Absorbed trivalent antimony readily enters red blood cells and accumulates primarily in the spleen, liver and bone. No sex-or age-related differences in antimony concentrations were found.
In vitro experiments with human blood have shown that Antimony accumulated in the red blood cells of rats repeatedly exposed to antimony potassium tartrate via drinking water; concentrations of antimony measured in organs were much lower (spleen, liver >kidneys >brain, fat).
Lauwers et al (1990) estimated that the total body antimony pool in a patient who died following accidental antimony potassium tartrate ingestion was only five per cent of the ingested dose with high antimony concentrations in the liver, gall bladder and gastrointestinal mucosa. This is consistent with antimony undergoing enterohepatic circulation.
In two studies with rodents, the portion of the total body burden of antimony in the lungs was calculated with the help of isotope-labeled antimony. It was found that <1% was in the lungs 2 hours after inhalation exposure to an aerosol of trivalent or pentavalent antimony tartrate

Details on excretion:

Antimony compounds are eliminated mainly in the urine, with small amounts appearing in faeces via bile after conjugation with glutathione.

Metabolites identified:

no

Executive summary:

Antimony and compounds, considered suitable for read-across to Potassium Sodium Tartrate is absorbed by inhalation and ingestion and accumulates in red blood cells, the spleen, liver and bones. The main excretion pathway for antimony is reported to be via the kidneys.

Cross-reference 2

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

acute toxicity: dermal

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

Justification for type of information:

structural similarities.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

no guideline followed

Principles of method if other than guideline:

The method used for skin absorption toxicity was essentially that of SMYTH, H. F. Jr. CARPENTER,C. P.. 'Well. C.S.. POZZANI. U.C. and STRIEGEL. J. A. ( 1962).
Range-finding toxicity data: List VI. .-irner. Ind. lfyg. As.r. J, 23. 955 107.

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

female

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The test material was applied in the amount of 0.5 g for solids and 0.5 ml for liquids or aqueous solutions. Aqueous solutions were made up by diluting pure materials or concentrated solutions to give percentages by weight. Solid materials were applied as powders. The material was applied to the designated patch areas and covered by a l-in.
square of surgical gauze two single layers thick. The gauze patches were held in place with strips of Elastoplast tape. The entire area was covered with a latex rubber film and secured with more Elastoplast tape.

Duration of exposure:

4 h

No. of animals per sex per dose:

3

Control animals:

not specified

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 20 000 mg/kg bw

Based on:

test mat. (total fraction)

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Conclusions:

The results are indicated as Single Skin Penetration DL50, yielding a value of 20000 mg/Kg.

Data source

Reference

Reference Type:

publication

Title:

Acute toxicity and skin corrosion data for some organic and inorganic compounds and aqueous solutions

Author:

E.H.Vernot, J.D.MacEwen, C.C. Haun, and E.R.Kinkead

Year:

1977

Bibliographic source:

University of California, Irvine, Toxic Hazards Research Unit, Overlook Branch, Dayton, Ohio 45431 USA

Materials and methods

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Fumaric acid

EC Number:

203-743-0

EC Name:

Fumaric acid

Cas Number:

110-17-8

Molecular formula:

C4H4O4

Test material form:

not specified

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

female

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Skin corrosion was tested using rabbits that had been clipped of all possible hair on backs and flanks 24 hr prior to exposure to allow for recovery of the skin from any irritation resulting from clipping. Six areas on the back, three on each side, were designated as patch areas to allow for the simultaneous testing of six materials per rabbit with six rabbits used for replicate testing of each series. Six areas on the back, three on each side, were designated as patch areas to allow for the simultaneous testing of six materials per rabbit with six rabbits used for replicate testing of each series. The material was applied to the designated patch areas and covered by a l-in.square of surgical gauze two single layers thick. The gauze patches were held in place with strips of Elastoplast tape. The entire area was covered with a latex rubber film and secured with more Elastoplast tape.

Duration of exposure:

4 h

Doses:

Single skin penetration of 0.5g

Control animals:

not specified

Results and discussion

Effect levels

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 20 000 mg/kg bw

Applicant's summary and conclusion

Conclusions:

Not classified

Executive summary:

Antimony Potassium tartate, like other salts of tartaric acid has very low Kow, a very high water solubility (ca. 83 g/L)

and is is mostly ionised at phisiological pH. According to the description made in section 7.1. and to the indication in part 7a of the CSR

Guidance Document, passage through the stratum corneum of the skin of this substance is very unlikely. Taking into account that the

substance has not a high toxicity and is rapidly degraded or excreted, the performance of dermal toxicity tests is not warranted. Thereby it is not considered justified to perform a dermal toxicity test, although it is recognised that dermal exposure during manufacture and handling cannot be excluded.