Antimony sulphide

Endpoint summary

Description of key information

Value used for CSA:

Bioaccumulation potential: no bioaccumulation potential

Absorption rate - oral (%): 0.05-0.3

Absorption rate - dermal (%): 0.1

Absorption rate - inhalation (%): <<1%

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

0.3

Absorption rate - dermal (%):

0.1

Additional information

Overview and quality of the database:

The majority of published data on toxicokinetics of antimony substances summarised in this dossier were generated several decades before the establishment of standardised test guidelines, and thus obviously do not correspond to current requirements. However, they nevertheless represent supportive data, from which the following conclusions can be drawn:

 

- for highly water-soluble antimony substances such as tartar emetic (potassium antimony tartrate), exact figures for oral absorption are difficult to derive. This is related to several experimental shortcomings, such as lack of a mass balance, inadequate description of dose and test item, and mostly indirect conclusions based on urinary excretion, for example. Therefore, these data at best allow rough estimates of absorbed/excreted amounts as supportive data. Nevertheless, the available published data support the assumption that absorption via the oral route is in the range of 1-5% of the dose for highly water soluble antimony substances.

 

- calculations based on a comparison of daily dietary intake of Sb, and the total Sb body burdens of stable Sb isotopes in humans (such as Caughtrey et al. 1983) suggest an oral absorption of up to 1% for Sb compounds, regardless of their origin and speciation; however, since Sb(V) is the predominant stable valence state under ambient environmental conditions and therefore the most predominant species in drinking water and diet, this calculation is likely to be biased on the grounds that Sb(V) is likely to be more bioavailable than Sb(III) species.

 

- for poorly water-soluble substances such as diantimony trioxide (approx. 5-6 orders of magnitude lower in water solubility than antimony trichloride, for example), published data are not available; for this reason, reference is made to a relative bioavailability study specifically with diantimony trioxide in rats (de Bie et al., 2005), which was conducted under GLP and in full OECD guideline compliance. This study is also of highest relevance to any rat study, since it covers the entire dose range (100-1,000 mg/kb bw) for any animal oral studies likely to be conducted, yielding oral absorption rates of 0.3% (at 100 mg/kg bw) and 0.05% (at 1,000 mg/kg bw), respectively.

  

Oral absorption:

 

Published data on oral absorption largely pertain to potassium antimony tartrate (also known as tartar emetic) and/to antimony trichloride. Both substances are highly water soluble, and in particular complexes of antimony with tartaric or citric acid are known to be stable and highly soluble, and thus have been used in the past in attempts to enhance the solubility/bioavailability of antimony, for example in pharmaceutical preparations:

species / test system	dose / test substance	oral absorption	comments	reliability score	references
mice/ rats/ monkeys oral (gavage) and i.v dosing	8-32 mg/kg bw ^124Sb Tartar emetic^(1)	oral absorption mice (single dosing 4.6-7.9%, rep. dosing 5%. (assessment for rats/monkeys incomplete)	Oral absorption assessment based on cumulative urinary excretion; Mass balance 80% (mice)	RL=2	Waitz et al. (1965)
rat	Sb Tartar emetic^(1)	absorption~ 5%	(2)	RL=3	Moskalev (1964), sec. citation from Coughtrey et al. (1983), and ICRP (1996)
mouse oral dosing (gavage)	not specified	Absorption max. 1-2% ICRP states “much less than 10%)	Sec. lit (2) No further data available		Walker (1970), sec. citation from Thomas et al. (1973)
hamster oral dosing (gavage)	2 µCi (not further specified) ^124Sb tartrate	Absorption < 1% estimated by ICRP based on fractional retention in GI tract	Exact dose not given, but very low since carrier-free tracer used	RL=2	Felicetti et al. (1974)
human route not stated	^124Sb tartrate	Absorption ~ 1% ICRP states “much less than 10%)	Sec. lit (2) No further data available		Rose & Jacobs (1969) sec. citation from Coughtrey et al. (1983)
human (f) ingestion	dose unknown/ Sb sulphide	Absorption < 5% value not stated in the publication, but estimated as an upper limit by ICRP based on blood and urine levels	attempted suicide with unknown amount of Sb2S3	RL=2	Bailly et al. (1991): sec. citation from Coughtrey et al. (1983)
rats oral dosing (gavage)	dose unknown ^125SbCl3	Whole body retention: ~ 1% for adults and 25d weanlings 40% for 5d sucklings	Exact dose not given, but very low since carrier-free tracer used	RL=4	Inaba et al. (1984)
mouse via diet	18.5 MBq/kg ^125SbCl3	1.7% calculated for suckling mice	Exact dose not given, but very low since carrier-free tracer was used	RL=4	Gerber et al. (1982)
dog oral dosing (capsules)	Nuclear debris (undefined)	> 4%	dose not given	RL=4	Chertok & Lake (1970)

(1): tartar emetic: potassium antimony tartrate; (2): cited from secondary literature (review)

Furthermore there is one study in which the oral absorption of soluble pentavalent antimony compounds is assessed to be less than 1% (Felicetti, 1974), based upon which ICRP (1981) concluded 1% oral absorption for all pentavalent antimony compounds.

Tissue distribution and elimination:

From published data on soluble antimony substances, it is known that any antimony becomes systemically available in blood with some impact of valence state upon blood partitioning. Antimony (III) is strongly associated with erythrocytes while antimony (V) preferentially partitions to plasma In the few available published studies addressing the aspect of tissue distribution, the highest levels were reported in thyroid, livers, kidney and spleen – other organs are in most cases not comprehensively studied. One very old study (Cowie, 1945) reports levels of 13 and 19 ug/g tissue wet weight for thyroid and liver, respectively, but the analytical procedure casts some doubt on the precision of these values.

 

The key study for the assessment of tissue distribution and elimination characteristics is a fully guideline-compliant study by de Bie et al. (2005). In this study, 72 hours after a single oral dose of 1,000 mg/kg bw/d to male and female rats, ca. 0.008% of the dose were excreted via urine, with the balance (98.7-100%) representing material excreted via faeces; total tissue levels and residual carcass levels were 0.0003-0.0004% and 0.0017-0.0023%, respectively. The valence state of antimony will impact excretion routes – Sb (III) excretion is primarily fecal whereas urinary excretion is the dominant route of excretion for Sb (V) ions. The detailed tissue analysis yielded (among other tissues with general lower levels, in ng/g of tissue): bone marrow 1192-1996, thyroid 1507-2103, spleen 197-113, livers 41-64 and lungs 41-61 (male-female, respectively). With respect to organs of reproductive function, the following data can be summarised: testes 2.8 ng/g, prostrate 8.5 ng/g; uterus, 11.4 ng/g, ovaries 262 ng/g. In consideration of the very low total amount of antimony (0.0003-0.0004%) in organs altogether, the above values allow the reasonable assumption that organs of male and female reproduction do not represent target organs for antimony trioxide. The collective data indicate that antimony ions are not metabolized within the body but that changes in valence can occur – a slow conversion from Sb(V) to Sb (III) has been documented.