DOSE-DEPENDENT EFFECTS ON THE DISPOSITION OF MONOMETHYLARSONIC ACID AND DIMETHYLARSINIC ACID IN THE MOUSE AFTER INTRAVENOUS ADMINISTRATION
作者:
Michael F. Hughes Elaina M. Kenyon,
期刊:
Journal of Toxicology and Environmental Health, Part A
(Taylor Available online 1998)
卷期:
Volume 53,
issue 2
页码: 95-112
ISSN:1528-7394
年代: 1998
DOI:10.1080/009841098159385
出版商: Informa UK Ltd
数据来源: Taylor
摘要:
The organic arsenicals monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) are the primary metabolites of inorganic arsenic, a known human carcinogen. The objective of this study was to examine if dose would affect the excretion and terminal tissue disposition of MMA and DMA in the mouse. 14C-MMA (4.84 and 484 mumol/ kg) and-DMA ( 8.04 and 804 mumol/kg) were administered to female micevia the tail vein. The mice were placed in metabolism cages for collection of urine (1, 2, 4, 8, 12, and 24 h) and feces ( 24 h) . The animals were then sacrificed at 24 h and tissues were removed and analyzed for radioactivity. The urine was also analyzed for parent compound and metabolites. Urinary excretion of MMA- and DMA-derived radioactivity predominated over fecal excretion. Dose did not affect the overall urinary excretion of both compounds. However, fecal excretion was significantly lower in the low-dose MMA-treated animals as opposed to in the high-dose group, whereas in the high-dose DMA-treated group excretion was lower than in the low-dose DMA group. The retention of radioactivity was low ( <2% of dose) and the distribution pattern similar for both compounds, with carcass > liver >kidney > lung. The concentration of radioactivity (% dose/ g tissue) was greater in kidney than in liver, lung, and blood for both compounds. The distribution and concentration of MMA-derived radioactivity was significantly greater in the liver and lung of the high-dose group. The MMA-treated animals excreted predominantly MMA in urine and lower amounts of DMA (<10% of the dose). The percentage excreted as DMA was significantly higher in the low-dose MM A group. In the urine of DMA-treated anim als, an unstable metabolite and the parent compound were detected. Overall, it appears the dose of organic arsenical administered has a minimal effect on its excretion and terminal tissue disposition in the mouse. The rapid elimination and low retention of MMA and DMA explain in part their low acute toxicity.
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