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PubMed2003

Cobalt and antimony: genotoxicity and carcinogenicity.

The purpose of this review is to summarise the data concerning genotoxicity and carcinogenicity of Co and Sb. Both metals have multiple industrial and/or therapeutical applications, depending on the considered species. Cobalt is used for the production of alloys and hard metal (cemented carbide), diamond polishing, drying agents, pigments and catalysts. Occupational exposure to cobalt may result in adverse health effects in different organs or tissues. Antimony trioxide is primarily used as a flame retardant in rubber, plastics, pigments, adhesives, textiles, and paper. Antimony potassium tartrate has been used worldwide as an anti-shistosomal drug. Pentavalent antimony compounds have been used for the treatment of leishmaniasis. Co(II) ions are genotoxic in vitro and in vivo, and carcinogenic in rodents. Co metal is genotoxic in vitro. Hard metal dust, of which occupational exposure is linked to an increased lung cancer risk, is proven to be genotoxic in vitro and in vivo. Possibly, production of active oxygen species and/or DNA repair inhibition are mechanisms involved. Given the recently provided proof for in vitro and in vivo genotoxic potential of hard metal dust, the mechanistic evidence of elevated production of active oxygen species and the epidemiological data on increased cancer risk, it may be advisable to consider the possibility of a new evaluation by IARC. Both trivalent and pentavalent antimony compounds are generally negative in non-mammalian genotoxicity tests, while mammalian test systems usually give positive results for Sb(III) and negative results for Sb(V) compounds. Assessment of the in vivo potential of Sb2O3 to induce chromosome aberrations (CA) gave conflicting results. Animal carcinogenicity data were concluded sufficient for Sb2O3 by IARC. Human carcinogenicity data is difficult to evaluate given the frequent co-exposure to arsenic. Possible mechanisms of action, including potential to produce active oxygen species and to interfere with DNA repair systems, still need further investigation.

Animals↗
PubMed1998

Biovolatilization of antimony and sudden infant death syndrome (SIDS).

1. The aerobic filamentous fungus S. brevicaulis IMI 17297 methylated antimony from Sb2O3 substrate, with the formation of gaseous trimethylantimony (TMA). No evidence was found for the generation of other gaseous antimony compounds by this organism. 2. Biovolatilization of inorganic antimony was greatest during cultivation of the fungus on solid media at 25 degrees C, and occurred more readily from antimony (III) substrates than from antimony (V) substrates. 3. Under simulated cot environment conditions (CO2 enriched atmosphere, 33 degrees C) the fungus exhibited an altered morphology and a reduced capability to volatilize inorganic antimony from the pure compound. 4. No evidence of antimony biovolatilization from cot mattress PVC was found, unless antimony was released from PVC by heat treatment (at 80 or 100 degrees C). 5. These data suggest that normal cot environment conditions are non-optimal for volatilization of antimony by S. brevicaulis, and that Sb2O3 in cot mattress PVC is not bioavailable. 6. Cot mattress isolates of S. brevicaulis also volatilized antimony (not encapsulated by PVC), whereas those of other filamentous fungi (Penicillium spp., Aspergillus niger, Aspergillus fumigatus, Alternaria sp.) and of bacteria (Bacillus spp.) did not. 7. The oxidation products of TMA may be the true determinants of toxicity for biogenic antimony gases produced in an aerobic environment.

Antimony↗
PubMed1991

Genotoxicity of beryllium, gallium and antimony in short-term assays.

The genotoxicity of beryllium, gallium and antimony compounds was studied with the rec, Salmonella mutagenicity and SCE assays. In the rec assay, all the salts of the metals, BeCl2, Be(NO3)2, GaCl3, Ga(NO3)3, SbCl3, SbCl5, and an oxide, Sb2O3, had DNA-damaging activity. None of the compounds was mutagenic to Salmonella. In the SCE assays using V79 cells, 2 antimony(III) compounds, SbCl3 and Sb2O3, and 2 beryllium compounds, BeCl2 and Be(NO3)2, induced SCEs significantly. Sb2O3, slightly soluble in water, was positive in both the rec assay and the SCE assay at very low doses.

Animals↗
PubMed1978

Sampling and analytical methods for antimony and its compounds - a review.

A review of sampling and analytical procedures for antimony and its compounds is presented. Emphasis has been placed on those methods which have application to personal air or biological samples in industrial hygiene. Two analytical techniques in particular have been used most frequently--colorimetric and atomic absorption. A need for research to develop satisfactory solid sorbent sampling techniques for stibine and other volatile antimony compounds is evident.

Antimony↗
PubMed2002

Antimony and bismuth compounds in oncology.

The main group elements antimony and bismuth are used clinically, primarily for the treatment of Leishmaniasis (antimony) and ulcers (bismuth). Despite their medicinal efficacy, the exploration of the anti-cancer potential of antimony and bismuth compounds is not as well developed as for other metal-containing species. The results of cytotoxicity and anti-tumour screening for antimony(III), antimony(V) and bismuth(III) compounds are summarised in this review. While this is a relatively undeveloped field of research endeavour, promising anti-tumour activity has been reported, in particular for bismuth compounds.

Animals↗
PubMed1997

Can microorganisms convert antimony trioxide or potassium antimonyl tartrate to methylated stibines?

No evidence could be found for the production, in culture, of methylated antimony compounds from water-insoluble or soluble antimony derivatives by the aerobes, Scopulariopsis brevicaulis or Bacillus sp. or by anaerobes associated with cot mattress materials. The study does not support the hypothesis that volatile organoantimony compounds are a cause of cot deaths. Anaerobic cultures from a polluted pond generated trimethylstibine from potassium antimonyl tartrate.

Antimony↗
PubMed1993

Successful treatment of antimony-resistant visceral leishmaniasis with liposomal amphotericin B in patients infected with human immunodeficiency virus.

We describe two cases of visceral leishmaniasis in patients infected with human immunodeficiency virus (HIV); both cases were resistant to antimony compounds but were cured with liposomal amphotericin B, with no significant toxicity. A review of the previous reported cases of antimony-resistant visceral leishmaniasis in HIV-infected patients confirmed the effectiveness of treatment with liposomal amphotericin B, which directly targets infected macrophages and reaches high levels in plasma and tissue.

AIDS-Related Opportunistic Infections↗
PubMed1998

Effects of antimonial therapy on serum zinc, copper and iron concentrations in patients with cutaneous Leishmaniasis in Turkey.

The effects of cutaneous leishmaniasis (CL) infections on total content of the essential trace elements and alterations of these elements content during antimonial therapy, serum iron (Fe), copper (Cu) and zinc (Zn), were determined in 40 patients with CL. 32 healthy subjects were selected as control group. Pentavalent antimonial compounds (Glucantime) were given intramuscularly (20 mg/kg/day) for three weeks in patients group. Serum Cu and Zn levels were determined by flame atomic absorption spectrometry and Fe levels were determined by colorimetrically. Before antimonial therapy; Cu levels were found significantly higher. However, Zn and Fe levels were found significantly lower in the patients group than those of controls. Cu levels were found tended to decrease, while Zn and Fe levels tended to increase during antimonial therapy. There was a negative correlation between serum Cu and Zn levels in CL patients (r = -0.322, p < 0.05). The findings showed that CL affects the essential trace element content and these changes began to disappear during antimonial therapy.

Adolescent↗
PubMedDate not supplied

Fate of antimony in municipal solid waste incineration.

The average antimony concentration in municipal solid waste is estimated to be about 10-60 ppm. Thermodynamical models predict a volatile behavior for antimony compounds, yet literature mass balances show that about 50% of the antimony input remains in the grate ashes. This fact can be explained by the formation of thermally stable antimonates in the fuel bed due to interactions with alkali or earth-alkali metals. Thermogravimetric experiments revealed an increased thermal stability for antimony oxide in presence of oxygen and calcium oxide. Spiking experiments on the test incinerator TAMARA showed that chlorination processes have a strong effect on antimony volatilization whereas high fuel-bed temperatures and addition of antimony oxide only have a moderate effect. In the grate ashes, antimony shows a pH-depending leaching property, which is typical for anionic species. This fact supports the thesis that antimony is present in the grate ashes in an anionic speciation.

Journal Article↗
PubMed1968

Comparative trials of antimonial drugs in urinary schistosomiasis.

Chemotherapeutic trials in urinary schistosomiasis are described and discussed. Their design and conduct were based on recommended statistical techniques, now generally accepted as the most appropriate approach to the assessment of antischistosomal drugs.Randomization produced comparable host groups in whom multiple parasitic infection and radiological urinary tract damage were common. Treatment was with one of three antimonial compounds given at equivalent metallic dosage daily.Antimony sodium tartrate (AST) and antimony dimercaptosuccinate (TWSb) were equally efficient curatively but both produced many side-effects. Sodium antimonylgluconate (TSAG) was four-fifths as effective but tolerance was superior. Estimations of urinary antimony excretion showed that tissue retention of the metal was related to cure-rates and side-effects. It was concluded that none of the drugs were suitable for mass chemotherapy.More new non-toxic schistosomicides are urgently needed and for their assessment, the setting-up of multicentre trials, following international agreement on technical methods, is suggested.

Adult↗
PubMed1998

Post-kala-azar dermal leishmaniasis.

Post-kala-azar dermal leishmaniasis is a dermatosis which was described during the first quarter of this century. Most cases reported are from the Indian subcontinent and certain parts of Africa. The disease generally follows an attack of kala-azar, usually a few months to several years after the visceral disease has healed. The clinical picture is variable. In this report, we present a case of post-kala-azar dermal leishmaniasis in a 5-year-old Iranian boy who presented with multiple, asymptomatic, erythematous papules on his trunk and extremities and a brownish, figurate discoloration on his lower extremities, 4 years after an attack of kala-azar which was completely cured. Histopathological examination of one of the biopsied papules revealed multiple Leishman bodies. The patient was successfully treated with a pentavalent antimonial compound.

Antiprotozoal Agents↗
PubMed2004

Ranking of chemical substances based on the Japanese Pollutant Release and Transfer Register using partial order theory and random linear extensions.

In 1997 a Pollutant Release and Transfer Register (PRTR) pilot project was initiated in Japan. In 1998 the project was expanded and in 1999 a law concerning the establishment of a national PRTR was adopted. Data on the emissions of chemical substances are therefore now being reported on a continuous base. In relation to the PRTR project data on toxicity have been collected. In order to make efficient use of the collected information on emission and toxicity it is useful to group or rank the chemical substances according to the impact on human health and the environment. It has recently been argued that partial order theory (POT) in combination with the use of linear extensions (LE) may be the most objective way to create a linear rank. The methodology has been further expanded to handle larger data sets by the use of random linear extensions (RLE). In this paper the Japanese PRTR data are ranked using the POT/RLE methodology. An average rank is established for chemical substances in the 1998 and 1999 PRTR in Japan. The top 10 chemical substances in the 1998 PRTR are: dichlorvos, inorganic arsenic compounds, cobalt compounds, beryllium compounds, fenitrothion, disulfoton, parathion, diazinon, 4,4'-diamino-3,3'-dichlorodiphenylmethane and antimony compounds. The top 10 chemical substances from the 1999 PRTR are PCBs, lead compounds, fenitrothion, dichlorvos, disulfoton, inorganic arsenic compounds, chlorothalonil, thiobencarb, chromium and HCFC-141b. The descriptor having the highest influence on the ranking of the 1998 PRTR data is the production volume, which, however, is not given in the 1999 PRTR. Further, the disagreement between the ranking with the lack of toxicity data substituted with mean and maximum values, respectively, strongly indicates a general need for further toxicological investigations.

Data Interpretation, Statistical↗
PubMed2003

Treatment of Old World cutaneous leishmaniasis with intralesionally injected meglumine antimoniate using a Dermojet device.

Pentavalent antimonial compounds, the mainstay in the treatment of the various forms of leishmaniasis, have considerable toxicity, are difficult to administer and expensive. We describe a safe and efficient therapeutic modality using a spring-loaded and air-powered device for the intralesional injection of a high-velocity meglumine antimoniate microspray in a patient with cutaneous leishmaniasis.

Adolescent↗
PubMedDate not supplied

Glucantime resistant Leishmania promastigotes are sensitive to pentostam.

Growth inhibition in vitro tests were used to study the susceptibility to pentostam of different Leishmania strains involved in cutaneous and mucocutaneous leishmaniasis--one glucantime sensitive strain, three naturally glucantime resistant strains and one glucantime resistant line developed by in vitro drug exposure. Contrasting with the high degree of glucantime resistance, all strains were sensitive to pentostam. These differences suggest that there is some relationship between chemical structure and in vitro activity for these antimonial compounds. These data justify a clinical re-evaluation to compare therapeutic efficacy of glucantime and pentostam in the treatment of leishmaniasis.

Animals↗
PubMedDate not supplied

Arsenic(III), but not antimony(III), induces DNA-protein crosslinks.

Antimony compounds are supposed to resemble to arsenicals in some toxicological features. Comparative investigations with antimony and arsenic were performed to collect data on the genotoxicity of antimony, on which the knowledge is scarce. In comparison to trivalent arsenic, trivalent antimony proved to be five times less cytotoxic in the neutral red assay and one order of magnitude less genotoxic in the cytokinesis-block micronucleus test using V79 Chinese hamster cells. The data obtained in the comet assay showed that the As(III)-mediated generation of DNA-protein crosslinks and DNA strand lesions seem to be two independent processes. In contrast, Sb(III) induced DNA strand lesions but not DNA-protein crosslinks. Further studies will have to investigate whether the genotoxicity of Sb(III) is mediated by an inhibition of DNA repair as it seems to be the case for As(III).

Animals↗