scholarly journals Arsenic Speciation in Human Organs following Fatal Arsenic Trioxide Poisoning—A Case Report

1999 ◽  
Vol 45 (2) ◽  
pp. 301-306 ◽  
Author(s):  
Larbi Benramdane ◽  
Michele Accominotti ◽  
Laurent Fanton ◽  
Daniel Malicier ◽  
Jean-Jacques Vallon

Abstract The aim of this investigation was to study the distribution of arsenic species in human organs following fatal acute intoxication by arsenic trioxide. The collected autopsy samples of most organs were ground and dried, and the total arsenic was measured by electrothermal atomic absorption spectrometry (ETAAS). The arsenic species—inorganic arsenic, in the form of arsenite [As(III)] and arsenate [As(V)], and its metabolites [monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)]—were quantified by ETAAS after extraction with methanol/water (1:1, by volume) and separation by HPLC. The results indicate that after acute intoxication, the liver and kidneys show the highest concentrations of total arsenic and that the total concentration in blood is 7- to 350-fold less concentrated than in organs. In all organs, As(III) is the predominant species, and MMA is more concentrated than DMA. MMA and DMA are more prevalent in lipidic organs (49% of total arsenic) compared with other organs (25% of total arsenic). As(V) was found in small quantities in the liver, kidneys, and blood.

1985 ◽  
Vol 4 (2) ◽  
pp. 203-214 ◽  
Author(s):  
M.A. Lovell ◽  
J.G. Farmer

Trends in the urinary concentrations of the four arsenic species, pentavalent [As (V)] and trivalent [As (III)] inorganic arsenic, monomethylarsonic acid (MMAA) and dimethylarsinic acid (DMAA), were followed for several days subsequent to the acute intoxication of two human subjects by arsenic trioxide [As (III)2O3] and sodium orthoarsenate [Na2HAs(V)O4.7H2O], respectively, in unsuccessful suicide attempts. Total arsenic concentrations ranged from 1.6 to 18.7 mg/l. The increasing predominance of the less toxic methylated species, especially DMAA, after 3 or 4 days supports the concept of methylation as a natural detoxification mechanism as part of an overall reduction/methylation sequence involved in the biotransformation of inorganic arsenic by the human body. However, the additional possibility of oxidation of As(III) to As(V) in vivo under extreme immediate postingestion conditions is suggested by initial high urinary As(V) after arsenic trioxide intoxication. Relative proportions of As(V), As(III), MMAA and DMAA in both cases probably reflect species-dependent differences in rates of direct elimination and reactivity with tissues as well as the efficiency of methylation.


2018 ◽  
Vol 8 (19) ◽  
Author(s):  
Tom Murphy ◽  
Kongkea Phan ◽  
Emmanuel Yumvihoze ◽  
Kim Irvine ◽  
Ken Wilson ◽  
...  

Background. Arsenic bioaccumulation in rice is a global concern affecting food security and public health. Objective. The present study examined arsenic species in rice in Cambodia to characterize health risks with rice consumption and to clarify uncertainties with Codex guidelines. Methods. The present study collected 61 well water samples, 105 rice samples, 70 soil samples, and conducted interviews with 44 families in Preak Russey near the Bassac River and Kandal Province along the Mekong River in Cambodia. Analyses of metals, total arsenic and arsenic species were conducted in laboratories in Canada, Cambodia and Singapore. Results. Unlike in Bangladesh, rice with the highest total arsenic concentrations in Cambodia contains mostly organic arsenic, dimethylarsinic acid (DMA), which is unregulated and much less toxic than inorganic arsenic. The present study found that storing surface runoff in ditches prior to irrigation can significantly reduce the arsenic concentration in rice. It is possible to remove > 95% of arsenic from groundwater prior to irrigation with natural reactions. Conclusions. The provision of high quality drinking water in 2015 to Preak Russey removed about 95% of the dietary inorganic arsenic exposure. The extremes in arsenic toxicity that are still obvious in these farmers should become less common. Rice from the site with the highest documented levels of arsenic in soils and water in Cambodia passes current Codex guidelines for arsenic. Informed Consent. Obtained Competing Interests. The authors declare no competing financial interests.


1998 ◽  
Vol 44 (3) ◽  
pp. 539-550 ◽  
Author(s):  
Mingsheng Ma ◽  
X Chris Le

Abstract We developed and evaluated a method for the determination of μg/L concentrations of individual arsenic species in urine samples. We have mainly studied arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid (MMAA), and dimethylarsinic acid (DMAA) because these are the most commonly used biomarkers of exposure by the general population to inorganic arsenic and because of concerns over these arsenic species on their toxicity and carcinogenicity. We have also detected five unidentified urinary arsenic species resulting from the metabolism of arsenosugars. We combined ion pair liquid chromatography with on-line hydride generation and subsequent atomic fluorescence detection (HPLC/HGAFS). Detection limits, determined as three times the standard deviation of the baseline noise, are 0.8, 1.2, 0.7, and 1.0 μ/L arsenic for arsenite, arsenate, MMAA, and DMAA, respectively. These correspond to 16, 24, 14, and 20 pg of arsenic, respectively, for a 20-μL sample injected for analysis. The excellent detection limit enabled us to determine trace concentrations of arsenic species in urine samples from healthy subjects who did not have excess exposure to arsenic. There was no need for any sample pretreatment step. We used Standard Reference Materials, containing both normal and increased concentrations of arsenic, to validate the method. Interlaboratory studies with independent techniques also confirmed the results obtained with the HPLC/HGAFS method. We demonstrated an application of the method to the determination of arsenic species in urine samples after the ingestion of seaweed by four volunteers. We observed substantial increases of DMAA concentrations in the samples collected from the volunteers after the consumption of seaweed. The increase of urinary DMAA concentration is due to the metabolism of arsenosugars that are present in the seaweed. Our results suggest that the commonly used biomarkers of exposure to inorganic arsenic, based on the measurement of arsenite, arsenate, MMAA, and DMAA, are not reliable when arsenosugars are ingested from the diet.


2014 ◽  
Vol 77 (4) ◽  
pp. 665-669 ◽  
Author(s):  
SHOUHUI DAI ◽  
HUI YANG ◽  
XUEFEI MAO ◽  
JING QIU ◽  
QUANJI LIU ◽  
...  

In previous studies, inorganic arsenic and total arsenic concentrations in rice bran have been much higher than those in polished rice obtained from the same whole paddy rice. However, the arsenic species distribution between rice and bran is still unknown, especially for arsenite (AsIII) and arsenate (AsV). To characterize the arsenic species in rice and bran and explain the elevated concentrations of inorganic arsenic and total arsenic, four arsenic species, AsIII, AsV, dimethylarsinic acid, and monomethylarsonic acid, were evaluated. Rice and bran samples (n = 108) purchased from local markets in the People's Republic of China were analyzed using high-performance liquid chromatography with hydride generation and atomic fluorescence spectrometry and then microwave extraction. As expected, most of the arsenic was found in bran, with bran/rice ratios of 6.8 for total arsenic species and 6.4 for inorganic arsenic. Among four arsenic species, the maximum bran/rice ratio was 104.7 (335/3.2 μg kg−1) for AsV followed by 1.2 (69.2/56.1) for AsIII, 1.3 (6.7/5.2) for dimethylarsinic acid, and 4.0 (0.8/0.2) for monomethylarsonic acid. Thus, the large difference in arsenic concentration between rice and bran was mostly due to the difference in the AsV concentration, which account for 96 and 95% of the difference for total arsenic species and inorganic arsenic, respectively. Therefore, the possibility of AsV contamination in rice bran and its by-products needs more study. This study is the first in which concentrations of AsIII and AsV in rice and bran have been documented, revealing that a higher percentage of AsV occurs in bran than in rice.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4426-4426
Author(s):  
Kazuyuki Shigeno ◽  
Miki Kobayashi ◽  
Naohi Sahara ◽  
Satoki Nakamura ◽  
Shinya Fujisawa ◽  
...  

Abstract Background: The therapy with ATO induced high complete remission and maintained for long survival for patients with relapsed or refractory APL. While the clinical effect of ATO against APL was confirmed, its pharmacokinetics has yet to be clarified. In most reports on pharmacokinetics of ATO, the arsenic concentrations were measured as total arsenic. We investigated the pharmacokinetics of arsenic species in Japanese patients with relapsed or refractory APL treated with ATO. Patients and Methods: In the prospective study, from 12 patients with APL treated with ATO, the blood and urine for the pharmacokinetic data were collected and subsequently stored frozen until analysis. ATO (0.15 mg/kg) was intravenously administered once daily over 2 hours to until bone marrow remission to a maximum of 60 days. The plasma and urine were collected on day 1 and after 1, 2 and 4 weeks. Inorganic arsenic (AsIII and AsV) and the major metabolites monomethylarsonic acid (MAAV) and dimethylarsinic acid (DMAAV) in plasma and urine were quantified by HPLC/ICP-MS. Results: Ten of 12 patients (83%) achieved complete remission (CR). Six of ten (60%) who achieved CR were negative in the post-treatment RT-PCR test. For two patients the blood and urine were collected also during consolidation. The plasma concentrations of inorganic arsenic on day 1 reached the Cmax (mean 22.6±11.4 ng/mL) immediately after completion of administration followed by a biphasic elimination while the appearance of methylated metabolites in the blood was delayed. During the repeated administration, the plasma concentrations of inorganic arsenic reached the steady-state. The Cmax of inorganic arsenic on week 4 was similar (mean 23.2±10.2 ng/mL) but the elimination was delayed. As a result, the AUC increased about 2-fold (from mean 211.8±55.1 to 474.8±192.6 ng/mL), and the clearance declined (from 0.7±0.2 to 0.4±0.1 L/kg/h) but no marked change was observed in volume of distribution. In contrast, the MAAV and DMAAV concentrations increased in relation to increased administration frequency fold (from mean 3.1±1.6, 5.4±2.9 to 10.9±4.7, 21.4±12.3 ng/mL). The plasma concentrations of arsenobetaine, an organic arsenic compound derived from seafood, remained almost constant (about 2 mg/mL) during the study period. The urinary excretion rates of AsIII and AsV remained almost constant after week 1, suggesting that the steady-state was attained. In contrast, a tendency to increase with administration frequency was observed in the excretion rates of MAAV and DMAAV after week 4 (from mean 17.4±11.2, 19.4±8.5 to 19.6±10.0, 21.1±9.5 %). The total arsenic excretion rate remained at ~60% of dose after week 1. Conclusion: ATO is metabolized when administered intravenously to APL patients and methylated metabolites were promptly eliminated from the blood and excreted into urine after completion of administration, indicating no measurable accumulation of ATO in the blood.


Environments ◽  
2020 ◽  
Vol 7 (9) ◽  
pp. 68
Author(s):  
Min-hyuk Kim ◽  
Junseob Kim ◽  
Chang-Hyun Noh ◽  
Seogyeong Choi ◽  
Yong-Sung Joo ◽  
...  

Seaweed, a popular seafood in South Korea, has abundant dietary fiber and minerals. The toxicity of arsenic compounds is known to be related to their chemical speciation, and inorganic arsenic (iAs) is more detrimental than other species. Due to the different toxicities of the various chemical forms, speciation analysis is important for evaluating arsenic exposure. In this study, total arsenic (tAs) and six arsenic species (arsenite, arsenate, monomethylarsonic acid, dimethylarsinic acid, arsenobetaine, and arsenocholine) were analyzed in 180 seaweed samples. Although there were differences between seaweed species, the concentration of tAs was detected at levels ranging from 1 to 100 µg/g, and the distribution of six arsenic species differed depending on the seaweed species. No correlation between the concentration of iAs and tAs was found in most seaweed species. Through statistical clustering, hijiki and gulfweed were seen to be the seaweeds with the highest ratios of iAs to tAs. Using the iAs concentration data from the arsenic speciation analysis, a risk assessment of seaweed intake in South Korea was conducted. The margin of exposure values showed no meaningful risk for the general population, but low levels of risk were identified for seaweed consumers, with high intakes of gulfweed and hijiki.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Yu Zheng ◽  
Yuan-Fei Mao ◽  
Hui-Jin Zhao ◽  
Li Chen ◽  
Li-Ning Wang ◽  
...  

Abstract Background Arsenic trioxide [ATO, inorganic arsenite (iAsIII) in solution] plays an important role in the treatment of acute promyelocytic leukemia (APL). However, the long-term adverse effects (AEs) and the retention of arsenic among APL patients are rarely reported. In this study, we focused on arsenic methylation metabolism and its relationship with chronic hepatic toxicity, as we previously reported, among APL patients who had finished the treatment of ATO. Methods A total of 112 de novo APL patients who had completed the ATO-containing treatment were enrolled in the study. Arsenic species [iAsIII, inorganic arsenate (iAsV), and their organic metabolites, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)] in patients’ plasma, urine, hair and nails were detected by high-performance liquid chromatography combined with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). Eighteen single nucleotide polymorphisms (SNPs) of the arsenic (+ 3 oxidative state) methylation transferase (AS3MT) gene, which was known as the main catalyzer for arsenic methylation, were tested with the polymerase chain reaction method. Results The study showed the metabolic pattern of arsenic in APL patients undergoing and after the treatment of ATO, in terms of total arsenic (TAs) and four species of arsenic. TAs decreased to normal after 6 months since cessation of ATO. But the arsenic speciation demonstrated significantly higher portion of iAsIII in patient’s urine (40.08% vs. 1.94%, P < 0.001), hair (29.25% vs. 13.29%, P = 0.002) and nails (30.21% vs. 13.64%, P = 0.003) than the healthy controls’, indicating a decreased capacity of arsenic methylation metabolism after the treatment of ATO. Urine primary methylation index (PMI) was significantly lower in patients with both chronic liver dysfunction (0.14 vs. 0.28, P = 0.047) and hepatic steatosis (0.19 vs. 0.3, P = 0.027), suggesting that insufficient methylation of arsenic might be related to chronic liver disorders. Two SNPs (A9749G and A27215G) of the AS3MT gene were associated with impaired urine secondary methylation index (SMI). Conclusions The long-term follow-up of arsenic speciation indicated a decreased arsenic methylation metabolism and a probable relationship with chronic hepatic disorders among APL patients after the cessation of ATO. Urine PMI could be a monitoring index for chronic AEs of ATO, and the SNPs of AS3MT gene should be considered when determining the dosage of ATO.


1994 ◽  
Vol 77 (2) ◽  
pp. 441-445 ◽  
Author(s):  
O Jimenez de Blas ◽  
S Vicente Gonzalez ◽  
R Seisdedos Rodriguez ◽  
J Hernandez Mendez

Abstract A flow injection–hydride generation/atomic absorption spectroscopic method for the measurement of total urinary arsenic and for the selective determination of inorganic arsenic, monomethylarsonic acid (MMAA), and dimethylarsinic acid (DMAA) was developed. Destruction of the organic matrix is necessary to measure total arsenic content of urine samples. Digestion of this matrix with HNO3–H2SO4–H2O2 is described. The separation of inorganic, monomethylated, and dimethylated arsenic compounds in urine was performed with ion-exchange chromatography on AG 50 W-X8 resin. Detection limits of 2 ppb for each arsenic form and of 3 ppb for total arsenic in urine analyzed after mineralization were found. Recoveries in triplicate urine samples spiked with 10 ppb inorganic arsenic, 20 ppb MMAA, and 40 ppb DMAA were 93, 91, and 85%, respectively. The precision (relative standard deviation) of the method obtained in 10 replicate analyses of urine samples spiked with arsenic metabolites varied from 3.2 to 4.6%. This method is applicable to urine samples in studies relating to arsenic exposure and its monitoring.


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