Biomethylation of inorganic arsenic by the rat and some laboratory animals

Odanaka, Yoshitsugu; Matano, Osami; Goto, Shinko

doi:10.1007/bf01608138

Cited by 81 publications

(22 citation statements)

References 9 publications

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“…Unlike humans, the marmoset and guinea pig do not methylate arsenic, so they are poor models for arsenic toxicity studies (Healy et al,1999; Vahter,2002). Rats do have metabolic, distribution, and excretion functions similar to those in humans (Odanaka et al,1980; Vahter,1981) and have been valuable models for investigating the effects of arsenic (Davis et al,2000; Lin et al,2002), plus arsenic–selenium interactions (Spallholz et al,2004).…”

Section: Introductionmentioning

confidence: 99%

Pathological, immunological and biochemical markers of subchronic arsenic toxicity in rats

Nain

Smits

2010

Environmental Toxicology

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Subchronic exposure to arsenic in rats was investigated to identify sensitive indicators of subclinical toxicity in rats. Immunological, pathological, and biochemical bioindicators were examined in rats exposed to arsenic in their drinking water. Juvenile male Wistar rats were allocated to four treatment groups receiving 0, 0.4, 4, and 40 ppm of arsenite in drinking water for 18 wks. Besides daily monitoring for clinical signs of adverse health effects, clinical biochemistry, B-cell-mediated and innate immune responses, plus gross, and histopathology were examined. In vitro tests of oxidative damage to basic cellular constituents, lipids, proteins, and nucleic acids, were measured using thiobarbituric acid reacting substances (TBARS) assays, protein carbonyl formation, and 8-hydroxydeoxyguanosine (8-OHdG), respectively. Clinical changes in the rats were limited to decreased feed and water intake in the high- (40 ppm) dose group (P < 0.05), however, growth rate was not affected. Serum biochemical changes occurred in blood urea nitrogen, K(+) , Cl(-) , and alanine aminotransferase (ALT) from arsenic exposure. Immunotoxicity was evident through a dose-dependent suppression of the secondary antibody-mediated response to a T-cell-dependent antigen, keyhole limpet hemocyanin (KLH). Histopathology of the liver revealed marked fatty infiltration and vacuolization particularly evident in periacinar hepatocytes. This pattern of toxicopathology in the high-exposure group may be related to the significantly higher (P < 0.05) oxidative stress, demonstrated through lipid peroxidation (TBARS assay) in the rats exposed to 40 ppm arsenite. The present study revealed that young, growing rats exposed to arsenic for 18 wks tolerated exposures up to 4 ppm. At higher doses, there was evidence of hepatotoxicity, humoral immunity was compromised, and an adverse effect on hepatic organelle and cell membranes was evident through a dose dependent increased in oxidative stress.

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Section: Introductionmentioning

confidence: 99%

Pathological, immunological and biochemical markers of subchronic arsenic toxicity in rats

Nain

Smits

2010

Environmental Toxicology

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“…It has been established that the rat is different from other mammals in that it accumulates arsenic in the blood. 16,17 In our experience, rats accumulate arsenic in the blood up to 30-60 times more than guinea pigs when given the same amount of sodium arsenate and sodium arsenite, respectively. Therefore, rats could be used as sensitive indicators for body absorption of arsenicals.…”

Section: Bioavailability Studymentioning

confidence: 84%

Speciation and absolute bioavailability: risk assessment of arsenic-contaminated sites in a residential suburb in Canberra†

Ng¹,

Kratzmann²,

Qı³

et al. 1998

Analyst

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Watson is a fully developed suburb of some 30 years in Canberra (the capital city of Australia). A plunge dip using arsenical pesticides for tick control was operated there between 1946 and 1960. Chemical investigations revealed that many soil samples obtained from the study area contained levels of arsenic exceeding the current health-based investigation levels of 100 mg kg 21 set by the National Health and Medical Research Council in Australia. For the speciation study, nine composite samples of surface and sub-surface soils and a composite sample of rocks were selected. ICP-MS analysis showed that arsenic levels in these samples ranged from 32 to 1597 mg kg 21 . Chemical speciation of arsenic showed that the arsenite (trivalent) components were 0.32-56% in the soil and 44.8% in the rock composite samples. Using a rat model, the absolute bioavailability of these contaminated soils relative to As 3+ or As 5+ ranged from 1.02 to 9.87% and 0.26 to 2.98%, respectively. An attempt was made to develop a suitable leachate test as an index of bioavailability. However, the results indicated that there was no significant correlation between the bioavailability and leachates using neutral pH water or 1 m HCl. Our results indicate that speciation is highly significant for the interpretation of bioavailability and risk assessment data; the bioavailable fractions of arsenic in soils from Watson are small and therefore the health impact upon the environment and humans due to this element is limited.

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“…Although a similar percentage is absorbed by the rat, significantly lower amounts are excreted (Stevens et al, 1977;Vahter et al, 1984). This is due to the unique binding of DMA to rat hemoglobin, which results in retention of the compound (Stevens et al, 1977;Odanaka et al, 1980). The absorption of DMA by the hamster after oral administration is lower than for other species 96 M. F. HUGHES AND E. M. KENYON (Yamauchi & Yamamura, 1984).…”

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confidence: 87%

Dose-Dependent Effects on the Disposition of Monomethylarsonic Acid and Dimethylarsinic Acid in the Mouse After Intravenous Administration

Em²

1998

Journal of Toxicology and Environmental Health, Part A

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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 mice via 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 MMA group. In the urine of DMA-treated animals, 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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Biomethylation of inorganic arsenic by the rat and some laboratory animals

Cited by 81 publications

References 9 publications

Pathological, immunological and biochemical markers of subchronic arsenic toxicity in rats

Pathological, immunological and biochemical markers of subchronic arsenic toxicity in rats

Speciation and absolute bioavailability: risk assessment of arsenic-contaminated sites in a residential suburb in Canberra†

Dose-Dependent Effects on the Disposition of Monomethylarsonic Acid and Dimethylarsinic Acid in the Mouse After Intravenous Administration

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