Inorganic trivalent arsenical

Arsenic is a metalloid that belongs to group VA of the periodic table. It exists in three oxidation states metalloid (0), trivalent (-3 or -i- 3), and pentavalent (-1-5). The most common inorganic trivalent arsenic compounds are arsenic trioxide, sodium arsenite, and sodium trichloride. Pentavalent inorganic arsenic compounds are arsenic pentaoxide, arsenic acid, and arsenate (e.g., lead arsenate and calcium arsenate). In general, the toxicity of arsenic compounds is in the following order arsine > arsenites > arsenates > organic > elemental. 

Arsenic compounds are thought to exert their toxic effects by several modes of action. Interference with enzyme function may result from sulfhydryl group binding by trivalent arsenic or by substitution for phosphate. Inorganic arsenic or its metabolites may induce oxidative stress, alter gene expression, and interfere with cell signal transduction. Although on a... 

GSH reductase (Styblo et ah, 1997) and thioredoxin reductase (Lin eta/., 1999). The inhibition may be due to the interaction of trivalent arsenic with critical thiol groups in these molecules. A mechanism of toxicity of pentavalent inorganic arsenic, such as arsenate, is its reduction to a trivalent form, such as arsenite. The reduction of arsenate to arsenite occurs in vivo. Another potential mechanism is the replacement of phosphate with arsenate. 

Toxicity of the various arsenic compounds in mammals extends over a wide range, determined in part by unique biochemical actions of each compound, but also by absorbability and efficiency of biotransformation and disposition. Overall, arsines present the greatest toxic hazard, followed closely by arsenites (inorganic trivalent compounds). Inorganic pentavalent compounds are somewhat less toxic that arsenites, while the organic (methylated)... 

Inorganic arsenic is methylated in humans to monomethylarsonic acid, MMA(V), and dimethylarsinic acid, DMA(V), both of which are more rapidly excreted in urine than is inorganic arsenic - especially the trivalent form (As III, arsen-ite). Absorbed arsenate (As V) is reduced to trivalent arsenic (As III) (for a review, see Vahter 2000). Le etal. (2000a,b) also identified monomethylarsonous acid, MMA(III), in the urine of inhabitants from irmer Mongolia after a single oral administration of 300 mg sodium-dimercapto-l-propane sulfonate (DMPS). 

Most authors report higher tissue concentrations of antimony in the liver, kidney, and thyroid shortly after administration of antimony potassium tartrate to animals (Brady 1945, Westrick 1953). Unlike arsenic, inorganic trivalent antimony is not methylated in vivo but is excreted in the bile and urine after conjugation with glutathione... 

The toxicity of a given arsenical is related to the rate of its clearance from the body and therefore to its degree of accumulation in tissues. In general, toxicity increases in the sequence of organic arsenicals arsenicals contain arsenic covalently linked to a carbon atom, where arsenic exists in the trivalent or pentavalent state. Arsphenamine contains trivalent arsenic sodium arsanilate contains arsenic in the pentavalent form. The organic arsenicals usually are excreted more rapidly than are the inorganic forms. 

Most of the inorganic arsenic is metabolized in the body to methylated arsenic species. Methylation of arsenic involves a stepwise process of two-electron reduction of the pentavalent arsenic species [e.g., As(V), MMA(V), and DMA(V)] to the trivalent arsenic species [e.g., As(III), MMA(III), and DMA(III)], followed by oxidative addition of a methyl group to the trivalent arsenic (Scheme 1) (5,88). Glutathione, cysteine, and dithiothreitol can act as reducing agents, and S-adenosylmethionine (SAM) is the methyl donor. Dimeth-ylarsinous acid (V) [DMA(V)] is the usual end product detected in humans. Tri-methylarsine oxide (V) [TMAO(V)] and trimethylarsine (III) [TMA(III)] are the end products produced by some microorganisms TMAO(V) is also produced by rats and mice. 

Recent studies using cultured cells have shown that MMA(III) and DMA(lll) are at least as toxic as the inorganic arsenic species (97-102). The methylated trivalent arsenic species are also proposed to be the proximate or ultimate genotoxic forms of arsenic (103). Thus, there has been much interest in the determination of these metabolites in humans. The observation of MMA(III) and DMA(III) species in human urine, together with these studies on arsenic toxic effects, indicates that methylation of arsenic may not be entirely a detoxification process for humans, as previously believed (104,105). Toxicological consequences of MMA(lll) and DMA(III) in humans need to be further examined. 

A. Inorganic arsenic compounds. In general, trivalent arsenic (As ) is 2-10 times more acutely toxic than pentavalent arsenic (As ). However, overexposure to either form produces a similar pattern of effects, requiring the same clinical approach and management. 

The situation for contaminants, containing arsenic (lewisite, adamsite, and clarke-1) is distinct from the above one, but is not any better. The products of their hydrolysis are poorly water-soluble, but, what is more important, they are highly toxic. Therefore, if such contaminants get into a sea medium from the places of their burial, large areas of the seabed will be poisoned by highly toxic substances, in particular, by inorganic compounds of trivalent arsenic. Life will be impossible in these regions. 

Elemental arsenic and its insoluble compoimds are non-toxic, whereas soluble inorganic and organic forms of the element may be poisonous. Needless to say, the amount (or dose) matters a lot. Trivalent arsenic is often toxic, the most common form is arsenite (As03 ) salts. Pentavalent arsenates (AsO ) are less of a concern, many of them are insoluble. This is also tme in general the properties of a certain element (including toxicity) very much depend on the form (most commonly the oxidation state) found in the compound. Determining which of the possible forms occur in a sample is called speciation. 

Arsenic has found wide use in pesticides, herbicides, wood preservatives and desiccants. Arsenic exposure can thus occur in many circumstances including occupations e.g., coal mines and smelters), air and food. The toxicity of arsenic varies widely with different chemical forms. As(III), As(V), monomethylarsonic acid (MMA) and dimetihylarsenic acid (DMA) are the arsenic species studied most in the literature. Inorganic arsenics are more toxic than organoarsenicals, while trivalent arsenic compounds are more toxic than their pentavalent counterparts. MMA and DMA are the two main metabolites known to be toxic. 

HG in its simplest form allows the speciation of inorganic As and As For the speciation of samples containing more than these two hydride-active species, a combination with GC is necessary. Every arsenic species, with the exception of those carrying four carbon bonds, can be transformed into arsines by borohydride. Most of the arsines are volatile and can be separated by GC. Depending on the pH used during hydride formation a distinction between tri-and pentavalent arsenic is in most cases possible. Trivalent arsenic species form hydrides already at pH 7, whereas pentavalent ones are only reactive at pH 1 (Table 2). Measuring the same sample with both pHs... 

Inorganic forms arsenic are more acutely toxic than the organic arsenicals and the toxicity depends upon the oxidation state of arsenic. Conversion between the oxidation states of inorganic arsenic have been shown to occur both in the environment and in the animal body. Recent studies (Vahter and Norin, 1980 Vahter, 1981) have suggested that the differences between the toxicities of trivalent and pentavalent arsenic depend upon the extent of vivo biotransformation to methylated metabolites. Environmental oxidation favors the conversion of trivalent arsenic to pentavalent arsenic. Pentavalent arsenic may be partially reduced vivo to trivalent arse-noxide (R As 0), but it is the vivo reduction of arsenate to arsenite which accounts for both toxicity and antimicrobial actions (Harvey, 1975). Rumen microflora obtained from Holstein cows reduced arsenate to arsenite (Forsberg, 1978). Ginsberg (1965) demon-... 

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