Title: Significance of arsenic speciation in mammalian toxicology
Abstract: Arsenic is a metalloid widely distributed in the earth’s crust and inorganic arsenic has been classified by IARC as Group I carcinogen. Arsenic can exist in 4 valency states. Generally, arsenite and arsenate are the common chemical species found in many environmental matrices with the former being the more toxic form. Solubilities of arsenicals depend on the pH and the ionic environment. The metabolism of inorganic in humans involves stepwise reduction, methylation and oxidation resulting in monomethylated (MMA) and dimethylated arsenic (DMA) metabolites. It has been shown that the toxicity of arsenic is in the order of MMAIII >DMAIII ~ AsIII > AsV > >DMAV ~ MMAV >> arsenobetaine. Arsenic from seafood and other marine origin such as arsenobetaine, arsenocholine, arsenic sugars and arsenolipids are considered to be less toxic. However, slightly more toxic metabolite ((CH3)3As=O, TMAO) has been detected after consumption of certain relatively non-toxic arsenicals from seafood. Since arsenic bioavailability and toxicity depend upon the chemical forms and solubilities it is important to conduct arsenic speciation for the assessment of its potential risk. This paper discussed aspects of arsenic speciation in several environmental toxicology studies conducted in our laboratory.For the bioavailability studies, the uptake of arsenite and arsenate into the blood by rodent was different. Bioavailability varied with arsenic species in the soil. The uptake was in the order of sodium arsenite > calcium arsenite > sodium arsenate. The bioavailability of anthropogenic arsenic is higher than that of the geological source (e.g. mineral).Speciation by HPLC-ICP-MS and X-ray spectroscopy showed that more than 50% of the arsenic was arsenite within the fronds of Chinese Brake Fern used for phytoremediation of arsenic. Chronic exposure of this arsenic-loaded fern (6,000 mg/kg dw) to rats and guinea pigs did not produce significant pathological effects. This could be explained that arsenic as phytochelatin is not bioavailable or toxic or both. This speculation will require further investigation. MMAIII is more cytotoxic than sodium arsenate. We were the first to demonstrate the carcinogenicity of sodium arsenate in mice. We repeated the life-time bioassay of sodium arsenate using environmental relevant concentrations and included for the first time chronic exposure of MMAIII in the same study. Multiple tumours were observed in mice treated with either arsenate- or MMAIII-spiked drinking water at 0, 100, 250 and 500 μg/L. The tumour incidences were in a dose response manner. The severity of lesions observed in the MMAIII-treated mice was higher suggesting that MMAIII might be a more potent carcinogen. The finding also suggests that MMAIII could be the proximal carcinogen of inorganic arsenic.
Publication Year: 2010
Publication Date: 2010-01-01
Language: en
Type: article
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