Arsenic Abstracts 1

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Do arsenosugars pose a risk to human health? The comparative toxicities of a trivalent and pentavalent arsenosugar

         (Andrewes, Demarini et al. 2004) Download

Seafood frequently contains high concentrations of arsenic (approximately 10-100 mg/kg dry weight). In marine algae (seaweed), this arsenic occurs predominantly as ribose derivatives known collectively as arsenosugars. Although it is clear that arsenosugars are not acutely toxic, there is a possibility of arsenosugars having slight chronic toxicity. In general, trivalent arsenicals are more toxic than their pentavalent counterparts, so in this work we examine the hypothesis that trivalent arsenosugars might be significantly more toxic than pentavalent arsenosugars in vitro. We compared the in vitro toxicity of (R)-2,3-dihydroxypropyl-5-deoxy-5-dimethylarsinoyl-beta-D-riboside, a pentavalent arsenosugar, to that of its trivalent counterpart, (R)-2,3-dihydroxypropyl-5-deoxy-5-dimethylarsino-beta-D-riboside. The trivalent arsenosugar nicked plasmid DNA, whereas the pentavalent arsenosugar did not. The trivalent arsenosugar was more cytotoxic (IC50 = 200 microM, 48 h exposure) than its pentavalent counterpart (IC50 > 6000 microM, 48 h exposure) in normal human epidermal keratinocytes in vitro as determined via the neutral red uptake assay. However, both the trivalent and the pentavalent arsenosugars were significantly less toxic than MMA(III), DMA(III), and arsenate. Neither the pentavalent arsenosugar nor the trivalent arsenosugar were mutagenic in Salmonella TA104. The trivalent arsenosugar was readily formed by reaction of the pentavalent arsenosugar with thiol compounds, including, cysteine, glutathione, and dithioerythritol. This work suggests that the reduction of pentavalent arsenosugars to trivalent arsenosugars in biology might have environmental consequences, especially because seaweed consumption is a significant environmental source for human exposure to arsenicals.


Elevated urine arsenic: un-speciated results lead to unnecessary concern and further evaluations

         (Kales, Huyck et al. 2006) Download

The consumption of seafood within two to three days of testing can increase total urine arsenic concentrations. Few clinicians are familiar with this fact and often misinterpret elevated results. A retrospective chart review of all cases with arsenic testing seen between 1991 and 2004 at an occupational and environmental medicine referral clinic was performed. Urine arsenic results were classified as follows: total arsenic levels; speciated results (inorganic, ionic arsenic); and whether the patient abstained from seafood prior to the collection. Laboratory detection limits for total and for ionic arsenic were < or = 2 microg/L. Fifty-four patients with urine arsenic testing were identified. The total urine arsenic concentration exceeded 40 microg/L for 28 patients. On paired, speciated testing (n = 21), mean total arsenic was 122 +/- 227 microg/L, and ionic arsenic was not detected in any of these same samples (p = 0.023). On paired testing, before and after seafood abstention (n = 12), total urine arsenic without abstention was 291 +/- 267 microg/L, and it was only 9 +/- 12 microg/L after seafood abstention (p = 0.004). The total urine arsenic elevations observed in our series were due to benign organic arsenic compounds commonly found in seafood. Laboratories should reflexively perform speciation on most samples with elevated total arsenic concentrations prior to reporting the results. Reflexive speciation could reduce unnecessary referrals, further testing, and patient anxiety.


Mineral arsenicals in traditional medicines: orpiment, realgar, and arsenolite

         (Liu, Lu et al. 2008) Download

Mineral arsenicals have long been used in traditional medicines for various diseases, yet arsenic can be highly toxic and carcinogenic. Arsenic in traditional medicines typically comes from deliberate addition for therapeutic purposes, mainly in the form of mineral arsenicals, including orpiment (As2S3), realgar (As4S4), and arsenolite (contains arsenic trioxide, As2O3). Inorganic arsenic is now accepted in Western medicine as a first line chemotherapeutic agent against certain hematopoietic cancers. This perspective analyzes the pharmacology and toxicology of these arsenicals used in traditional medicines. Orpiment and realgar are less soluble and poorly absorbed from the gastrointestinal tract, whereas the bioavailability of arsenic trioxide is similar to inorganic arsenic salts such as sodium arsenite. Pharmacological studies show that arsenic trioxide and realgar are effective against certain malignancies. Orpiment and realgar are used externally for various skin diseases. Realgar is frequently included as an ingredient in oral traditional remedies for its antipyretic, anti-inflammatory, antiulcer, anti-convulsive, and anti-schistosomiasis actions, but the pharmacological basis for this inclusion still remains to be fully justified. Toxicological studies show that cardiovascular toxicity is the major concern for arsenic trioxide and that the gastrointestinal and dermal adverse effects may occur after prolonged use of mineral arsenicals. Little is known regarding the possible secondary cancers resulting from the long-term use of any of these arsenicals. Similar to the safety evaluation of seafood arsenicals, total arsenic content alone appears to be insufficient for mineral arsenical safety evaluation. Arsenic speciation, bioavailability, and toxicity/benefit should be considered in evaluation of mineral arsenical-containing traditional medicines.


Arsenic in seaweed--forms, concentration and dietary exposure

         (Rose, Lewis et al. 2007) Download

This study has measured the content of total and inorganic forms of arsenic in seaweed available on retail sale for consumption, to provide data for dietary exposure estimates and to support advice to consumers. A total of 31 samples covering five varieties of seaweed were collected from various retail outlets across London and the internet. All of the samples were purchased as dried product. For four of the five varieties, soaking was advised prior to consumption. The recommended method of preparation for each individual sample was followed, and total and inorganic arsenic were analysed both before and after preparation. The arsenic remaining in the water used for soaking was also measured. Arsenic was detected in all samples with total arsenic at concentrations ranging from 18 to 124 mg/kg. Inorganic arsenic, which can cause liver cancer, was only found in the nine samples of hijiki seaweed that were analysed, at concentrations in the range 67-96 mg/kg. Other types of seaweed were all found to contain less than 0.3mg/kg inorganic arsenic, which was the limit of detection for the method used. Since consumption of hijiki seaweed could significantly increase dietary exposure to inorganic arsenic, the UK Food Standards Agency (FSA) issued advice to consumers to avoid eating it.


References

Andrewes, P., D. M. Demarini, et al. (2004). "Do arsenosugars pose a risk to human health? The comparative toxicities of a trivalent and pentavalent arsenosugar." Environ Sci Technol 38(15): 4140-8. [PMID: 15352453]

Kales, S. N., K. L. Huyck, et al. (2006). "Elevated urine arsenic: un-speciated results lead to unnecessary concern and further evaluations." J Anal Toxicol 30(2): 80-5. [PMID: 16620536]

Liu, J., Y. Lu, et al. (2008). "Mineral arsenicals in traditional medicines: orpiment, realgar, and arsenolite." J Pharmacol Exp Ther 326(2): 363-8. [PMID: 18463319]

Rose, M., J. Lewis, et al. (2007). "Arsenic in seaweed--forms, concentration and dietary exposure." Food Chem Toxicol 45(7): 1263-7. [PMID: 17336439]