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Determination of arsenic in urine and feces by dry ashing, atomic absorption spectrometry.

A dry ashing flameless atomic absorption procedure was used to determine fish-arsenic in human urine and feces. Samples were dry ashed with Mg(NO3)2--MgO and dissolved in 6N HCl. Arsine was generated by the addition of NaBH4 and swept into a thermally heated silica tube furnace. Recoveries of several arsenic compounds added to samples ranged from 85 to 117%. The detection limit was about 3 ppb as for 10 g sample. Effects of the presence of common cations, anions and acids were studied.

Animals↗

Use of a luminescent bacterial biosensor for biomonitoring and characterization of arsenic toxicity of chromated copper arsenate (CCA).

An arsenic oxyanion-inducible Escherichia coli chromosomal operon (arsRBC) has been previously identified. Construction of a luciferase transcriptional gene fusion (arsB::luxAB) showed that ars operon expression, plus concomitant cell luminescence, was inducible in a concentration-dependent manner by arsenic salts. The present study was conducted to evaluate the potential of the arsB::luxAB transcriptional gene fusion for use as a biosensor in monitoring the toxicity of arsenic compounds. Cultures from this gene fusion strain were exposed to increasing concentrations of the wood preservative chromated copper arsenate (CCA), as well as its constituents, sodium arsenate and chromated copper solution (CC). Analysis of luciferase activity revealed that the arsB::luxAB gene fusion was expressed in response to CCA and sodium arsenate, but not to the CC solution. The detection limit of arsenic was found to be 0.01 microgram As/ml (10 parts per billion, 10 ppb) and therefore well within the range of environmental concerns. A greater induction of luminescence by arsenate was observed when cells were limited for phosphate, as phosphate can act as a competitive inhibitor of arsenate ions. Our results suggest that the E. coli arsB::luxAB fusion strain has a promising future as a specific and sensitive biosensor for monitoring bioavailable levels and toxicity of arsenic near sites where CCA-treated wood has been used.

Arsenates↗

[Effect of arsenic on the developing brain of rat (author's transl)].

An experiment was conducted in an attempt to determine the effect of arsenic on body weight, brain weight and brain chemical composition in suckling rats. Four hundred and ninety-nine young rats from Wistar albino mothers in a closed colony (TAMURA, 1950) were grouped into four according to the treatment given. Group 1 served as control. Rats in Group II were treated with As2O3 1.5 mg/kg, those in Group III 15 mg/kg and those in Group IV arsenic compounds (corresponding 15 mg/kg of As2O3) for 7 to 21 days after birth. Measurements were recorded for 3 to 15 weeks. The mortality of groups I and II was approximately 10%, while that of groups III and IV was approximately 50%. Regarding body weight, brain weight and brain chemical composition of provision of the same, there was no significant difference between controls and the arsenic treated males and females under conditions Oriental feed diet and powdered milk.

Animals↗

Arsenic-copper interaction in the kidney of the rat: influence of arsenic metabolites.

The present study was an attempt to investigate whether the renal accumulation of Cu observed in the kidneys of rats and guinea-pigs exposed to arsenite (As-III) was an effect of arsenite alone or also shared by its metabolites--arsenate (As-V), dimethylarsinic acid and monomethylarsonic acid. The four arsenic compounds were administered subcutaneously and separately to rats for 12 days in increasing doses. Kidney, liver and blood were taken and analysed for As, Cu and other trace elements by atomic emission spectrometry. Results indicate that administration of As-V leads to renal Cu accumulation similar to that observed on administration of As-III and that the accumulation in both cases is dependent on the dose of arsenic, although higher doses of As-V were required to achieve renal Cu levels comparable to that of As-III. A constant molar As:Cu ratio independent of arsenic dose was obtained in the kidney. Dimethylarsinic acid did not affect renal Cu levels at all. Administration of monomethylarsonic acid led to a slight increase in renal Cu levels which did not increase further in spite of increased doses of monomethylarsonic acid. It is concluded from these studies that neither the metabolic transformation of inorganic arsenic to its methylated products nor its metabolites (dimethylarsinic acid and monomethylarsonic acid) caused the observed renal Cu accumulation, rather, the inorganic form of As, either in the trivalent or pentavalent form is responsible.

Animals↗

Photodegradation of roxarsone in poultry litter leachates.

Arsenic compounds have been used extensively in agriculture in the US for applications ranging from cotton herbicides to animal feed supplements. Roxarsone (3-nitro-4-hydroxyphenylarsonic acid), in particular, is used widely in poultry production to control coccidial intestinal parasites. It is excreted unchanged in the manure and introduced into the environment when litter is applied to farmland as fertilizer. Although the toxicity of roxarsone is less than that of inorganic arsenic, roxarsone can degrade, biotically and abiotically, to produce more toxic inorganic forms of arsenic, such as arsenite and arsenate. Experiments were conducted on aqueous litter leachates to test the stability of roxarsone under different conditions. Laboratory experiments have shown that arsenite can be cleaved photolytically from the roxarsone moiety at pH 4-8 and that the degradation rate increases with increasing pH. Furthermore, the rate of photodegradation increases with nitrate and natural organic matter concentration, reactants that are commonly found in poultry-litter-water leachates. Additional photochemical reactions rapidly oxidize the cleaved arsenite to arsenate. The formation of arsenate is not entirely undesirable, because it is less mobile in soil systems and less toxic than arsenite. A possible mechanism for the degradation of roxarsone in poultry litter leachates is proposed. The results suggest that poultry litter storage and field application practices could affect the degradation of roxarsone and subsequent mobilization of inorganic arsenic species.

Animals↗

Quadruple cancer including Bowen's disease after arsenic injections 40 years earlier: report of a case.

This report describes the successful treatment of quadruple cancer including Bowen's disease in a 71-year-old man who had been given injections of salvarsan, an arsenic compound, for syphilis more than 40 years earlier. Resection of a skin lesion on his chest subsequently confirmed a diagnosis of Bowen's disease, 3 years after which he was operated on for concurrent gastric cancer and sigmoid colon cancer. A fourth cancer was discovered on his left vocal cord 2 weeks after this operation; it was resected 2 years later. A discussion of multiple malignant neoplasms and the possible relationship between arsenic and cancer is presented following this case report.

Adenocarcinoma↗

Isolation and preliminary toxicological evaluation of arsenobetaine - the water-soluble arsenical constituent from the hepatopancreas of the western rock lobster.

The water soluble arsenic compound present in the hepatopancreas of the western rock lobster (Panulirus cygnus George) has been isolated as the reineckate salt and has been identified as arsenobetaine. Intraperitoneal injection of arsenobetaine into mice at 500 mg kg-1 did not result in mortality, and no symptoms of poisoning were observed. Mice treated with arsenobetaine at 360 mg kg-1 rapidly eliminated the compound in their excreta and no evidence was obtained for metabolic alteration. When tested in the Ames' Salmonella typhimurium system for chemical mutagens, both in the presence and absence of liver microsomal oxidase fraction, arsenobetaine gave consistently negative results.

Animals↗

Effect of indigenous bacterial activity on arsenic mobilization under anaerobic conditions.

Batch biochemical leaching tests were carried out to investigate the mobility of arsenic from a contaminated soil collected from a French gold mining site. The specific objective of this research was to examine the effect of indigenous bacterial activity on arsenic mobilization under anaerobic conditions. In a first step, physical and chemical characterizations were performed to provide data concerning the liquid-solid partitioning and mobility of arsenic and other inorganic constituents. In a second step, batch bioleaching tests were conducted in shaker flasks to determine the effect of indigenous bacterial activity under different anaerobic conditions (i.e., addition of mineral nutrients and carbon sources) on arsenic mobilization. Results indicated that arsenic release during contact with deionized water was limited by its very low solubility in the interstitial solution and by the stability of the different arsenic compounds formed with the amorphous solid phases of the soil (mainly iron (oxy)hydroxides). However, an increased mobilization potential was observed over the long term under anaerobic conditions with indigenous bacterial activity enhanced by the addition of carbon sources.

Arsenic↗

Evaluation of the in vitro activity and in vivo bioavailability of realgar nanoparticles prepared by cryo-grinding.

Arsenic trioxide (As2O3) has been a research focus because of its promising anticancer effects especially in the treatment of leukemia. Another arsenic compound, realgar (As2S2), has long been used as a therapeutic agent to treat some diseases in ancient China and Europe, and its medicinal effects have attracted increasing attentions in recent years. However, its poor water-solubility unfortunately results in poor bioavailability and hampers it from being studied and used for possible clinical application. In this study, nanosized realgar particles were prepared by cryo-grinding with polyvinylpyrrolidone (PVP) and/or sodium dodecyl sulfate (SDS). Major physical properties of the respective nanosized realgar particles were characterized. Co-grinding realgar with PVP and/or SDS produced smaller and more monodisperse suspension of nanoparticles. The in vitro cytotoxic effects of such nanosized realgar particles on selected human ovarian (CI80-13S, OVCAR, OVCAR-3) and cervical (HeLa) cancer cell lines were investigated. Significant anti-proliferation effect of these realgar nanoparticles on these cancer cell lines was observed. CI80-13S was most sensitive to the nanosized realgar particles with IC50 values of less than 1 microM as As2S2, whereas the other cancer cell lines had IC50 values in a range of 2-4 microM as As2S2. The cytotoxic activity of the realgar nanoparticles to these human gynecological cell lines was comparable to arsenic trioxide observed previously. In these cancer cell lines, the cytotoxic effects were caused by apoptosis as confirmed by cell cycle and DNA laddering analysis. In in vivo study, a remarkable increase in urinary recovery of arsenic was observed in rats after a single oral administration of the cryo-ground realgar particle suspension. Ranging from 58.5 to 69.6% of the administered dose of arsenic was recovered in urine in the first 48 h from the PVP and/or SDS co-ground preparations; whereas the original realgar powder gave a urinary recovery of only 24.9%. The finding suggested that size reduction of realgar particles to nano levels could enhance its bioavailability substantially.

Animals↗

Accumulation and elimination of dietary arsenobetaine in two species of fish, Atlantic salmon (Salmo salar L.) and Atlantic cod (Gadus morhua L.).

Despite the fact that marine fish contain relatively high concentrations of the naturally occurring arsenic compound arsenobetaine, little is known about the disposition of arsenobetaine in fish. We investigated the accumulation, distribution, and elimination of dietary arsenobetaine in Atlantic salmon (Salmo salar L.) and Atlantic cod (Gadus morhua L.), with the focus on muscle, liver, and kidney tissues. The fish were exposed to dietary arsenobetaine (24.7 +/- 0.6 microg As/g feed) for three months, followed by a three-month depuration period. The two species showed marked differences in the accumulation and elimination of arsenobetaine. Total arsenic concentrations in Atlantic salmon increased significantly in muscle, liver, and kidney, whereas in Atlantic cod, a significant increase in total arsenic concentration was observed only in muscle. Elimination kinetics in muscle were distinct between the two species, with elimination half-lives from muscle tissue estimated at approximately 77 d in Atlantic cod and 37 d in Atlantic salmon, resulting in an absorption efficiency approximately twofold higher in Atlantic cod (15 +/- 1%) compared to that in Atlantic salmon (8 +/- 1%). The differences in arsenobetaine disposition studied in Atlantic salmon and Atlantic cod contribute to explain the differences in arsenic levels observed among marine fish.

Animals↗

Metabolism of arsenocholine in mice, rats and rabbits.

The distribution, retention and biotransformation of arsenocholine, an organic arsenic compound present in certain seafood, have been studied in rats, mice and rabbits by use of synthesized 73 As-labelled arsenocholine. Orally administered arsenocholine was almost completely absorbed from the gastro-intestinal tract in mice and rats. In all species 70--80% of the administered dose was excreted in the urine within 3 days, [73 As] arsenobetaine was the main urinary metabolite; [73 As] arsenocholine was found in the urine of the first day only. No degradation to inorganic arsenic, mono- or dimethylarsenic acids, or trimethylarsine oxide was observed. In the tissues the 73 As activity retained was found in the form of [73 As] arsenobetaine and [73 As arsenophospholipids. Tissues with longest retention times were prostate, epididymis, testes, myocardium, liver, adrenal cortex, pancreas, dental pulp and pituitary gland.

Animals↗

Conversion of adamsite (phenarsarzin chloride) by fungal manganese peroxidase.

Fungal manganese peroxidase was found to convert the persistent chemical warfare agent adamsite (phenarsarzin chloride) in a cell-free reaction mixture containing sodium malonate, Mn(2+) ions, and reduced glutathione. The organo-arsenical compound disappeared completely within 48 h accompanied by the formation of a more polar metabolite with a clearly modified UV spectrum. Thus, As(III) in the adamsite molecule was oxidized by manganese peroxidase to As(V) which added dioxygen and released chloride.

Arsenicals↗

[Malignant diseases of the inner nose--epidemiology and occupational medicine aspects].

Squamous cell carcinomas are the most frequent malignancies of the inner nose, followed by adenocarcinomas, adenoid cystic carcinomas, and other malignant neoplasms. Carcinomas of the nose can be recognized as occupational diseases if there has been a professional exposition to ionizing rays, certain arsenic compounds, hexavalent chrome compounds, nickel, oak or beech wood dust. The sources of danger relevant in industrial medicine are indicated. At present, adenocarcinomas induced by dust of wood are of special significance: 16 out of 22 carcinomas of the nose recognized as occupational diseases between 1978 and 1986 are due to oak and beech wood dust.

Adenocarcinoma↗

Toxicity, bioavailability and metal speciation.

1. Environmental toxicology emphasizes the difference from traditional toxicology in which pure compounds of interest are added to purified diets, or injected into the test animals. When the objective is to study the fate and effects of trace elements in the environment, knowledge of the speciation of the elements and their physico-chemical forms is important. 2. Cadmium salts such as the sulfides, carbonates or oxides, are practically insoluble in water. However, these can be converted to water-soluble salts in nature under the influence of oxygen and acids. Chronic exposure to Cd is associated with renal toxicity in humans once a critical body burden is reached. 3. The solubility of As(III) oxide in water is fairly low, but high in either acid or alkali. In water, arsenic is usually in the form of the arsenate or arsenite. As(III) is systemically more poisonous than the As(V), and As(V) is reduced to the As(III) form before exerting any toxic effects. Organic arsenicals also exert their toxic effects in vivo in animals by first metabolizing to the trivalent arsenoxide form. Some methyl arsenic compounds, such as di- and trimethylarsines, occur naturally as a consequence of biological activity. The toxic effect of arsenite can be potentiated by dithiols, while As has a protective effect against the toxicity of a variety of forms of Se in several species. 4. Selenium occurs in several oxidation states and many selenium analogues of organic sulfur compounds exist in nature. Selenium in selenate form occurs in alkaline soils, where it is soluble and easily available to plants. Selenite binds tightly to iron and aluminum oxides and thus is quite insoluble in soils. Hydrogen selenide is a very toxic gas at room temperature. The methylated forms of Se are much less toxic for the organism than selenite. However, the methylated Se derivatives have strong synergistic toxicity with other minerals such as arsenic. 5. Aquatic organisms absorb and retain Hg in the tissues, as methylmercury, although most of the environmental Hg to which they are exposed is inorganic. The methylmercury in fish arises from the bacterial methylation of inorganic Hg. Methylmercury in the human diet is almost completely absorbed into the bloodstream. The nervous system is the principal target tissue affected by methylmercury in adult human beings, while kidney is the critical organ following the ingestion of Hg(II) salts.

Animals↗

Benefits of high resolution IC-ICP-MS for the routine analysis of inorganic and organic arsenic species in food products of marine and terrestrial origin.

A recently developed and validated method for simultaneous determination of 17 inorganic and organic arsenic compounds in marine biota has been successfully applied to routine analysis of different food products, including fish, shellfish, edible algae, rice, and other types of grain. During one year, approximately 250 food samples were analyzed, mostly fish and rice. Long-term stability and robustness of the system was observed and reproducible results for certified reference materials were ensured by means of control charts. The separation was performed by ion-pair chromatography on an anion-exchange column to separate anionic, neutral, and cationic arsenic species in one chromatographic run. Hyphenation to ICP-MS allowed element-specific and sensitive detection of the different arsenic species with a detection limit as low as 8 ng As L(-1 )in the sample extract, which is equivalent to 2 ng As g(-1) in the original sample. Special emphasis was laid on the analysis of marine algae and rice samples. These food types can contain elevated levels of the very toxic inorganic arsenic species (up to 90% in rice) and therefore are the focus of interest in the food industry. In marine algae, inorganic arsenic was mainly present as arsenate whereas in rice arsenite predominated.

Arsenicals↗

Arsenic and SCE in human lymphocytes.

The effects of tri- and penta-valent arsenic compounds on sister-chromatid exchange (SCE) in both G0 and 5-bromodeoxyuridine (BrdU) substituted chromosomes was investigated. ¿Of 4 donors whose lymphocytes were exposed to sodium arsenate for 2 cell cycles 1 showed an increase, 2 a decrease, and 1 neither an increase or decrease over baseline levels. Exposure to sodium arsenite produced a similar result with 2 of 4 donors showing a significant increase in SCE. G0 lymphocytes exposed to either sodium arsenate or sodium arsenite did not show increased SCE. These results indicate that although arsenic can induce SCEs in human lymphocytes, there is considerable variation in SCE response among individuals. Furthermore, the data suggest that the increased SCEs seen in patients exposed to arsenic may be due to the patient's condition and not arsenic exposure.

Arsenates↗

Arsenic trioxide as an inducer of apoptosis and loss of PML/RAR alpha protein in acute promyelocytic leukemia cells.

BACKGROUND: Retinoids, which are derivatives of vitamin A, induce differentiation of acute promyelocytic leukemia (APL) cells in vitro and in patients. However, APL cells develop resistance to retinoic acid treatment. Arsenic trioxide (As2O3) can induce clinical remission in patients with APL, including those who have relapsed after retinoic acid treatment, by inducing apoptosis (programmed cell death) of the leukemia cells. In this study, we investigated the molecular mechanisms by which As2O3 induces apoptosis in retinoic acid-sensitive NB4 APL cells, in retinoic acid-resistant derivatives of these cells, and in fresh leukemia cells from patients. METHODS: Apoptosis was assessed by means of DNA fragmentation analyses, TUNEL assays (i.e., deoxyuridine triphosphate labeling of DNA nicks with terminal deoxynucleotidyl transferase), and flow cytometry. Expression of the PML/RAR alpha fusion protein in leukemia cells was assessed by means of western blotting, ligand binding, and immunohistochemistry. Northern blotting and ribonuclease protection assays were used to evaluate changes in gene expression in response to retinoic acid and As2O3 treatment. RESULTS AND CONCLUSIONS: As2O3 induces apoptosis without differentiation in retinoic acid-sensitive and retinoic acid-resistant APL cells at concentrations that are achievable in patients. As2O3 induces loss of the PML/RAR alpha fusion protein in NB4 cells, in retinoic-acid resistant cells derived from them, in fresh APL cells from patients, and in non-APL cells transfected to express this protein. As2O3 and retinoic acid induce different patterns of gene regulation, and they inhibit the phenotypes induced by each other. Understanding the molecular basis of these differences in the effects of As2O3 and retinoic acid may guide the clinical use of arsenic compounds and provide insights into the management of leukemias that do not respond to retinoic acid.

Antineoplastic Combined Chemotherapy Protocols↗

Pesticides and cancer.

Epidemiologic evidence on the relationship between chemical pesticides and cancer is reviewed. In animal studies, many pesticides are carcinogenic, (e.g., organochlorines, creosote, and sulfallate) while others (notably, the organochlorines DDT, chlordane, and lindane) are tumor promoters. Some contaminants in commercial pesticide formulations also may pose a carcinogenic risk. In humans, arsenic compounds and insecticides used occupationally have been classified as carcinogens by the International Agency for Research on Cancer. Human data, however, are limited by the small number of studies that evaluate individual pesticides. Epidemiologic studies, although sometimes contradictory, have linked phenoxy acid herbicides or contaminants in them with soft tissue sarcoma (STS) and malignant lymphoma; organochlorine insecticides are linked with STS, non-Hodgkin's lymphoma (NHL), leukemia, and, less consistently, with cancers of the lung and breast; organophosphorous compounds are linked with NHL and leukemia; and triazine herbicides with ovarian cancer. Few, if any, of these associations can be considered established and causal. Hence, further epidemiologic studies are needed with detailed exposure assessment for individual pesticides, taking into consideration work practices, use of protective equipment, and other measures to reduce risk.

Animals↗