The metabolism of inorganic arsenic oxides, gallium arsenide, and arsine: a toxicochemical review.
The aim of this review is to compare the metabolism, chemistry, and biological effects to determine if either of the industrial arsenicals (arsine and gallium arsenide) act like the environmental arsenic oxides (arsenite and arsenate). The metabolism of the arsenic oxides has been extensively investigated in the past 4 years and the differences between the arsenic metabolites in the oxidation states +III versus +V and with one or two methyl groups added have shown increased importance. The arsenic oxide metabolism has been compared with arsine (oxidation state -III) and arsenide (oxidation state between 0 to -III). The different metabolites appear to have different strengths of reaction for binding arsenic (III) to thiol groups, their oxidation-reduction reactions and their forming an arsenic-carbon bond. It is unclear if the differences in parameters such as the presence or absence of methyl metabolites, the rates of AsV reduction compared to the rates of AsIII oxidation, or the competition of phosphate and arsenate for cellular uptake are large enough to change biological effects. The arsine rate of decomposition, products of metabolism, target organ of toxic action, and protein binding appeared to support an oxidized arsenic metabolite. This arsine metabolite was very different from anything made by the arsenic oxides. The gallium arsenide had a lower solubility than any other arsenic compound and it had a disproportionate intensity of lung damage to suggest that the GaAs had a site of contact interaction and that oxidation reactions were important in its toxicity. The urinary metabolites after GaAs exposure were the same as excreted by arsenic oxides but the chemical compounds responsible for the toxic effects of GaAs are different from the arsenic oxides. The review concludes that there is insufficient evidence to equate the different arsenic compounds. There are several differences in the toxicity of the arsenic compounds that will require substantial research.
Carter
Dean E
DE
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721-0207, USA. gandolfi@pharmacy.arizona.edu
Aposhian
H Vasken
HV
Gandolfi
A Jay
AJ
D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005708:Gallium / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D019055:No-Observed-Adverse-Effect Level; D016273:Occupational Exposure / Q000009:adverse effects*; D010087:Oxides / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity
D001152:Arsenicals; D010087:Oxides; D014874:Water Pollutants, Chemical; C043055:gallium arsenide; D005708:Gallium; D000077237:Arsenic Trioxide; C006633:arsine