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Massive arsenic poisoning--effect of hemodialysis and dimercaprol on arsenic kinetics.

In massive arsenic poisoning, the use of hemodialysis and dimercaprol (BAL) therapy is still controversial. Hemodialysis is thought of value only for supportive care. BAL therapy has been criticized because of its delayed action, its own toxicity and its possible influence on arsenic clearance during hemodialysis. We studied arsenic kinetics during an acute suicidal intoxication (10 g of sodium arsenate). Treatment included gastric lavage, oral charcoal and supportive measures. Hemodialysis was performed immediately and repeated the next day. BAL therapy was prescribed only on the second day. Cardiovascular collapse, anuria and hepatic disturbance recovered in a few days and the patient could be discharged on the 15th day. Instantaneous serum arsenic hemodialysis clearance was 85 +/- 75 ml/min without previous BAL injection and 87.5 +/- 75 ml/min with a previous 250 mg BAL injection (difference not significant) indicating that BAL did not impede arsenic dialysis. The calculated total hemodialysis clearance of arsenic was higher than mean serum hemodialysis clearance indicating that erythrocyte bound arsenic is also eliminated during dialysis. We propose to consider early hemodialysis as an elimination measure in massive arsenic poisoning and to choose BAL as a chelator when dialysis is required.

Adult↗

Arsenic-related skin lesions and glutathione S-transferase P1 A1578G (Ile105Val) polymorphism in two ethnic clans exposed to indoor combustion of high arsenic coal in one village.

OBJECTIVES: A total of 2402 patients with arsenic-related skin lesions, such as hyperkeratosis, hyperpigmentation or hypopigmentation, or even skin cancer in a few villages in Southwest Guizhou Autonomous Prefecture, China represent a unique case of endemic arsenism related with indoor combustion of high arsenic coal. This study aimed to investigate the cluster of arsenism cases and the possible relevant factors including GSTP1 polymorphism in two clans of different ethnic origin living in one village for generations. METHODS: A questionnaire-based study was performed in 170 Miao clan P members, 10 of whom had arsenic-related skin diseases, and 153 Han clan G1 members, 50 of whom had arsenic-related skin diseases. The data were checked against the registration archives since the 1980s. At the same time, arsenic concentrations in samples of coal, indoor air, drinking water, corn and chilli pepper that were once baked over the stoves for desiccation, as well as in samples of urine and hair of clan members were determined. Glutathione S-transferase P1 (GSTP1) A1578G polymorphism was genotyped by a restriction fragment length polymorphism-based procedure. RESULTS: Arsenism morbidity in Miao clan P was significantly lower than in the neighbouring Han clan G1 [5.9 vs. 32.7%, odds ratio (OR)=0.13, 95% confidence interval (CI): 0.06-0.27, P<0.0001]. No sex differences were confirmed inside both clans. Analyses of the environmental samples indicated that Miao clan P members were exposed to higher amounts of arsenic via inhalation and food ingestion. Hair and urine samples also proved a higher arsenic body burden in ethnic Miao individuals. No corresponding differences by sex were found. Higher frequencies of combined mutant genotype G/G1578 and A/G1578 (OR=4.72, 95% CI: 2.34-9.54, P<0.0001) and of mutant allele G1578 (OR=3.22, 95% CI: 2.00-5.18, P<0.0001) were detected in diagnosed arsenism patients than in non-diseased individuals. The Miao individuals showed a lower percentage of combined mutant genotypes (30.6 vs. 52.7%, OR=0.40, 95% CI: 0.19-0.84, P=0.015) as well as of mutant allele G1578 (OR=0.46, 95% CI: 0.24-0.88, P=0.017) than their Han neighbours. CONCLUSIONS: Genetic predisposition influences dermal arsenism toxicity. The GSTP1 A1578G (Ile105Val) status might be a susceptibility factor for arsenic-related skin lesions.

Adolescent↗

Clinical pharmacokinetic study of arsenic trioxide in an acute promyelocytic leukemia (APL) patient: speciation of arsenic metabolites in serum and urine.

The pharmacokinetics of arsenic species in a Japanese patient with relapsed acute promyelocytic leukemia (APL) treated with arsenic trioxide at a daily dose of 0.08 mg/kg was investigated. After achieving complete remission on Day 35 during the induction therapy of arsenic trioxide, we collected the serum and urine samples on Days 4 and 5 during the consolidation therapy of arsenic trioxide. The concentrations of inorganic arsenic and the methylated metabolites in serum and urine were measured by HPLC/ICP-MS. The patient restricted taking the seafood for 3 d before the start of administration and during the sampling period in order to avoid the influence of arsenic derived from seafood. Arsenite (As(III)), methylarsonic acid (MMAs(V)), and dimethylarsinic acid (DMAs(V)) were detected in serum and urine. The total concentration of As(III), MMAs(V) and DMAs(V) in serum ranged from 18 to 41 microg/l (240-547 nM) during 24 h on Day 4. The amount of total arsenic (As(III)+MMAs(V)+DMAs(V)) in urine was 4464 microg/d on Day 4. These results suggest that not the micro-molar but the nano-molar order of arsenic in serum is sufficient to produce the therapeutic effect on APL cells.

Aged↗

Arsenic excretion after treatment of arsenic poisoning with DMSA or DMPS in mice.

The effects of 2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid, Na salt (DMPS) on arsenic excretion in arsenic poisoning were studied using ICR mice. One group of mice was given arsenic trioxide (5 mg As/kg, s.c.) and another two groups were given DMSA or DMPS (100 mg/kg, i.p.) immediately after administration of the arsenic (5 mg/kg, s.c.). Arsenic excretion in urine and feces was determined by atomic absorption spectrophotometry. Results obtained showed a marked arsenic excretion in the urine collected at the first 12 hr in the group treated with DMSA. Further remarkable arsenic excretion in the feces was seen in the group treated with DMPS, suggesting that arsenic might have been excreted in the bile.

Animals↗

Status of groundwater arsenic contamination and human suffering in a Gram Panchayet (cluster of villages) in Murshidabad, one of the nine arsenic affected districts in West Bengal, India.

A detailed study was carried out in a cluster of villages known as Sagarpara Gram Panchayet (GP), covering an area of 20 km2 and population of 24,419 to determine the status of groundwater arsenic contamination and related health effects. The arsenic analysis of all hand tubewells (n = 565) in working condition showed, 86.2% and 58.8% of them had arsenic above 10, and 50 microgl(-1), respectively. The groundwater samples from all 21 villages in Sagarpara GP contained arsenic above 50 microgl(-1). In our preliminary clinical survey across the 21 villages, 3,302 villagers were examined and 679 among them (20.6%) were registered with arsenical skin lesions. A total of 850 biological samples (hair, nail and urine) were analysed from the affected villages and, on average, 85% of them contained arsenic above the normal level. Thus, many people of Sagarpara might be sub-clinically affected. Our data was compared with the international one to estimate population in Sagarpara GP at risk from arsenical skin lesions and cancer. Proper watershed management and economical utilization of available surface water resources along with the villagers' participation is urgently required to combat the present arsenic crisis.

Adult↗

Arsenic sorption by carbonate-rich aquifer material, a control on arsenic mobility at Zimapán, México.

Arsenic retention by carbonate-rich aquifer material at Zimapán, México, was studied to gain insight into the processes controlling arsenic mobility in natural systems. Batch experiments showed that retention of soluble As (V) on carbonate-rich aquifer material was 35.3-90% in the pH range of 7-9 found in Zimapán natural water. Chemical and mineralogical compositions, point of zero charge (PZC), and experimental arsenic retention at various pH of three composite samples of limestone (M1, M2, M3) showed that sorption (adsorption and coprecipitation) may be one of the main processes controlling arsenic mobility in the Zimapán As-polluted aquifer. The PZC values approximately corresponded to the PZC reported for the main minerals present in each sample: hydrous ferric oxides (M1), calcite (M2), and the range from hydrous ferric oxides and calcite (M3). The chemical and mineralogical compositions of each sample explain the obtained PZC values. Experimental and modeled arsenic retention at various pH values on sample M1 corresponded to reported arsenic adsorption onto hydrous ferric oxides. Coprecipitacion of complex Ca arsenates or arsenic adsorption onto calcite or clay minerals could be the main processes of arsenic retention on samples M2 and M3. Groundwater flow through the granular, carbonate-rich, shallow aquifer may decrease the water As content as a result of these interactions. A remediation method based on the promotion of polluted water flow into the shallow aquifer could be developed from these results.

Adsorption↗

Effects of heavy metals on growth and arsenic accumulation in the arsenic hyperaccumulator Pteris vittata L.

The effects of Cd, Ni, Pb, and Zn on arsenic accumulation by the arsenic hyperaccumulator Pteris vittata were investigated in a greenhouse study. P. vittata was grown for 8 weeks in an arsenic-contaminated soil (131 mg As kg(-1)), which was spiked with 50 or 200 mg kg(-1) Cd, Ni, Pb, or Zn (as nitrates). P. vittata was effective in taking up arsenic (up to 4100 mg kg(-1)) and transporting it to the fronds, but little of the metals. Arsenic bioconcentration factors ranged from 14 to 36 and transfer factors ranged from 16 to 56 in the presence of the metals, both of which were reduced with increasing metal concentration. Fern biomass increased as much as 12 times compared to the original dry weight after 8 weeks of growth (up to 19 g per plant). Greater concentrations of Cd, Ni, and Pb resulted in greater catalase activity in the plant. Most of the arsenic in the plant was present as arsenite, the reduced form, indicating little impact of the metals on plant arsenic reduction. This research demonstrates the capability of P. vittata in hyperaccumulating arsenic from soils in the presence of heavy metals.

Arsenic↗

Inhibition of insulin-dependent glucose uptake by trivalent arsenicals: possible mechanism of arsenic-induced diabetes.

Chronic exposures to inorganic arsenic (iAs) have been associated with increased incidence of noninsulin (type-2)-dependent diabetes mellitus. Although mechanisms by which iAs induces diabetes have not been identified, the clinical symptoms of the disease indicate that iAs or its metabolites interfere with insulin-stimulated signal transduction pathway or with critical steps in glucose metabolism. We have examined effects of iAs and methylated arsenicals that contain trivalent or pentavalent arsenic on glucose uptake by 3T3-L1 adipocytes. Treatment with inorganic and methylated pentavalent arsenicals (up to 1 mM) had little or no effect on either basal or insulin-stimulated glucose uptake. In contrast, trivalent arsenicals, arsenite (iAs(III)), methylarsine oxide (MAs(III)O), and iododimethylarsine (DMAs(III)O) inhibited insulin-stimulated glucose uptake in a concentration-dependent manner. Subtoxic concentrations of iAs(III) (20 microM), MAs(III)O (1 microM), or DMAs(III)I (2 microM) decreased insulin-stimulated glucose uptake by 35-45%. Basal glucose uptake was significantly inhibited only by cytotoxic concentrations of iAs(III) or MAs(III)O. Examination of the components of the insulin-stimulated signal transduction pathway showed that all trivalent arsenicals suppressed expression and possibly phosphorylation of protein kinase B (PKB/Akt). The concentration of an insulin-responsive glucose transporter (GLUT4) was significantly lower in the membrane region of 3T3-L1 adipocytes treated with trivalent arsenicals as compared with untreated cells. These results suggest that trivalent arsenicals inhibit insulin-stimulated glucose uptake by interfering with the PKB/Akt-dependent mobilization of GLUT4 transporters in adipocytes. This mechanism may be, in part, responsible for the development of type-2 diabetes in individuals chronically exposed to iAs.

Animals↗

Deposition and fate of arsenic in iron- and arsenic-enriched reservoir sediments.

Deposition of arsenic to the sediments of Haiwee Reservoir (Olancha, CA) has dramatically increased since March 1996 as a result of an interim strategy for arsenic management in the Los Angeles Aqueduct (LAA) water supply. Ferric chloride and cationic polymer are introduced into the Aqueduct at the Cottonwood treatment plant, 27 km north of the Haiwee Reservoir. This treatment decreases the average arsenic concentration from 25 microg/L above Cottonwood to 8.3 microg/L below Haiwee. Iron- and arsenic-rich flocculated solids are removed by deposition to the reservoir sediments. Analysis of sediments shows a pronounced signature of this deposition with elevated sediment concentrations of iron, arsenic, and manganese relative to a control site. Sediment concentrations of these elements remain elevated throughout the core length sampled (ca. 4% iron and 600 and 200 microg/g of manganese and arsenic, respectively, on a dry weight basis). A pore water profile revealed a strong redox gradient in the sediment. Manganese in the pore waters increased below 5 cm; iron and arsenic increased below 10 cm and were strongly correlated, consistent with reductive dissolution of iron oxyhydroxides and concurrent release of associated arsenic to solution. X-ray absorption near-edge spectroscopy revealed inorganic As(V) present only in the uppermost sediment (0-2.5 cm) in addition to inorganic As(III). In the deeper sediments (to 44 cm), only oxygen-coordinated As(III) was detected. Analysis of the extended X-ray absorption fine structure spectrum indicates that the As(III) at depth remains associated with iron oxyhydroxide. We hypothesize that this phase persists in the recently deposited sediment despite reducing conditions due to slow dissolution kinetics.

Absorptiometry, Photon↗

Development of a sampling train for arsenic in pyrolysis vapours resulting from pyrolysis of arsenic containing wood waste.

In the present study a sampling and analysis method for arsenic emissions during pyrolysis of arsenic containing wood, such as chromated copper arsenate (CCA) treated wood, has been developed. The procedure is based on the NIOSH (National Institute for Occupational Safety and Health) standard for arsenic trioxide sampling. Validation for this specific application is needed since pyrolysis of arsenic containing wood leads to a gas stream containing sticky tar compounds and aerosols. Validation was carried out through tube furnace experiments using both CCA treated wood and arsenic trioxide powder as input. The outlet of the tube furnace was coupled to a cooling section and sampling train. The sampling train consisted of one or more filter sections and impingers. Different combinations of filters (untreated or impregnated) and impingers, as well as different combinations of washing solutions were tested. The different units of the sampling train were analysed by inductively coupled plasma mass spectrometry (ICP-MS) in order to determine the distribution of arsenic over the different units. For the working conditions considered (pyrolysis at 350 degrees C for 20 minutes with a nitrogen flow rate of 100 Nl h(-1)) the combination of a quartz cooling tube and a cellulose ester membrane filter impregnated with a Na2CO3-glycerol solution was sufficient to capture the arsenic. Two extra impingers (the first one containing 50 ml HNO3 1 M in the case of CCA treated wood and 50 ml NaOH 0.1 M in the case of As2O3 and the second one containing 50 ml NaOH 0.1 M) were added downstream of the filter section as backup either in case of filter failure or to check whether all the arsenic released is captured by the cooling tube and filter.

Air Pollutants↗

Urinary arsenic, chromium, and copper levels in workers exposed to arsenic-based wood preservatives.

Urinary excretion of arsenic, chromium, and copper in workers exposed to arsenic-based wood preservatives was examined to evaluate occupational exposure to these chemicals. Spot urine samples were collected from 89 wood treaters and a comparison group of 232 individuals with no known exposure to arsenicals. The results of urinalysis revealed that the wood treaters averaged 103 micrograms arsenic/L while the comparison group averaged 74 micrograms arsenic/L. The mean urinary chromium and copper levels of the wood treaters were 41 micrograms chromium/L and 191 micrograms copper/L compared with 63 micrograms chromium/L and 221 micrograms copper/L for the comparison group. Covariance analysis of urinary arsenic level between the exposed and comparison groups revealed that the adjusted mean arsenic levels of the exposed population (78 to 122 micrograms arsenic/L) were significantly higher than that of the comparison group (72 micrograms arsenic/L). The adjusted mean urinary arsenic levels of these wood treaters, however, were within published normal limits. Analysis of covariance allowed comparison of group means after statistical adjustments for possible confounding variables such as seafood intake and age. The results indicate that urinary arsenic values can provide a useful index of occupational exposure to chromated copper arsenate wood preservatives, when the effects of dietary arsenic are controlled statistically.

Adult↗

EXAFS study on arsenic species and transformation in arsenic hyperaccumulator.

Synchrotron radiation extended X-ray absorption fine structure (SR EXAFS) was employed to study the transformation of coordination environment and the redox speciation of arsenic in a newly discovered arsenic hyperaccumulator, Cretan brake (Pteris cretica L. var nervosa Thunb). It showed that the arsenic in the plant mainly coordinated with oxygen, except that some arsenic coordinated with S as As-GSH in root. The complexation of arsenic with GSH might not be the predominant detoxification mechanism in Cretan brake. Although some arsenic in root presented as As(V) in Na2HAsO4 treatments, most of arsenic in plant presented as As(III)-O in both treatments, indicating that As(V) tended to be reduced to As(III) after it was taken up into the root, and arsenic was kept as As(III) when it was transported to the above-ground tissues. The reduction of As(V) primarily proceeded in the root.

Absorptiometry, Photon↗

[Hygienic evaluation of the effects of vibration and arsenic in miners engaged in extraction of arsenic-containing ore].

Hygienic evaluation covered work conditions on 4 gold mines including 3 ones for gold and arsenic and one "arsenic-free". The mines demonstrated similar occupational factors, but differed in arsenic content of the ore extracted and therefore in arsenic concentrations in air of the workplaces. Miners engaged into extraction of the arsenic-containing ore, especially those exposed to vibration and arsenic concentrations over the MAC, manifest extensive arsenic accumulation in the hair and excretion with the urine, higher morbidity with transitory disablement, more prevalent vibration disease and mortality with malignancies. Vibration disease in those subject has more severe course, serious vegetative and sensory polyneuropathy, that is believed to result from co-action of vibration and arsenic.

Air Pollutants, Occupational↗

Pharmacokinetics of arsenic species in Japanese patients with relapsed or refractory acute promyelocytic leukemia treated with arsenic trioxide.

PURPOSE: To investigate the pharmacokinetics of arsenic species in Japanese patients with relapsed or refractory acute promyelocytic leukemia (APL) treated with arsenic trioxide (ATO) at a daily dose of 0.15 mg/kg. METHODS: Inorganic arsenic (AsIII and AsV) and the major metabolites monomethylarsonic acid (MAA(V)) and dimethylarsinic acid (DMAA(V)) in plasma and urine collected from 12 Japanese patients were quantified by HPLC/ICP-MS. RESULTS: The plasma concentrations of AsIII and AsV on day 1 reached the similar Cmax (12.4 +/- 8.4 and 10.2 +/- 3.9 ng/ml) immediately after completion of administration followed by a biphasic elimination. The AUC(0-infinity) of AsV was about twice that of AsIII. The appearance of methylated metabolites in the blood was delayed. During the repeated administration, the plasma concentrations of inorganic arsenic reached the steady state. In contrast, the MAA(V) and DMAA(V) concentrations increased in relation to increased administration frequency. The mean total arsenic excretion rate including inorganic arsenic and methylated arsenic was about 20% of daily dose on day 1 and remained at about 60% of daily dose during week 1-4. CONCLUSIONS: This study demonstrates that ATO is metabolized when administered intravenously to APL patients and methylated metabolites are promptly eliminated from the blood and excreted into urine after completion of administration, indicating no measurable accumulation of ATO in the blood.

Adult↗

Arsenic speciation in the urine and hair of individuals exposed to airborne arsenic through coal-burning in Guizhou, PR China.

The extent of exposure of residents of Changqing (Guizhou, PR China) to arsenic through coal-burning was investigated. Despite the low coal-arsenic content (56.3+/-42.5 mg As kg(-1)) when compared with coals collected at different location and times from the same province, more than 30% of the study subjects have shown symptoms of arsenicosis. Coal, urine, hair, and water samples were collected in mid-September 2001 and analysed for arsenic. The average urinary and hair-arsenic concentrations in the exposed subjects were 71.4+/-37.1 microg As g(-1) creatinine (control 41.6+/-12.1) and 7.99+/-8.16 mg kg(-1), respectively. A positive correlation between the hair and urinary-arsenic concentration (R(2)=0.601) was found. There was no significant difference between females and males for both urinary and hair-arsenic concentrations. Females were found to have a higher dimethylarsinic acid but lower percentages of inorganic arsenic and monomethylarsonic acid in their urine than males.

Adult↗

Relation between airborne arsenic trioxide and urinary excretion of inorganic arsenic and its methylated metabolites.

The relation between exposure to As2O3 fumes and dust, and the urinary excretion of inorganic arsenic metabolites (monomethylarsonic acid, dimethylarsinic acid, unchanged inorganic arsenic) has been studied in 18 workers from a sulphuric acid producing plant. The concentration of arsenic in the breathing zone of each worker was measured during five consecutive days and urine samples were obtained after one shift and before the next. The collection efficiency of the air sampling system exceeded 95%. The time weighted average exposure (TWA) concentrations of As2O3 ranged from 6 to 502 micrograms As/m3 and were log normally distributed. Although exposure probably occurred by ingestion as well as inhalation, statistically significant correlations (log scales) were found between airborne TWA of As2O3 and the inorganic arsenic metabolites in urine collected immediately after the shift, or just before the next shift. For a TWA of 50 micrograms As/m3, the mean concentration of the sum of the three inorganic arsenic metabolites in a postshift urine sample amounted to about 55 micrograms arsenic/g creatinine (95% confidence interval (95% CI) 47-62). Higher estimates of urinary arsenic reported by other authors are probably due either to the influence of dietary organoarsenicals when total arsenic is measured in urine or to a low retention efficiency of the air sampling system for As2O3 in the vapour phase.

Adult↗

Differential determination of arsenic (III) and total arsenic with L-cysteine as prereductant using a flow injection non-dispersive atomic absorption device.

Speciation of arsenic in environmental samples gains increasingly importance, as the toxic effects of arsenic are related to its oxidation state. A method was developed for the determination of trace amounts of arsenic (III) and total arsenic by flow injection hydride generation coupled with an in-house made non-dispersive AAS device. The total arsenic is determined after prereduction of arsenic (V) to arsenic (III) with L-cysteine in a low concentration of hydrochloric, acetic or nitric acid. The conditions for the prereduction, hydride generation and atomization were systematically investigated. A quartz tube temperature of 800 degrees C was found to be optimum in view of peak shape and baseline stability. Pb(II), Ni(II), Fe(III), Cu(II), Ag(I), Al(III), Ga(II), Se(IV), Bi(III) were checked for interfering with the 2 microg/L As(V) signal. A serious signal depression was only observed for Se(IV) and Bi(III) at a 150-fold excess. With the above system, arsenic was determined at a sampling frequency of about 1/min with a detection limit (3sigma) of 0.01 microg/L using a 0.5 mL sample. The reagent blank was 0.001+/-0.0003 absorbance units and the standard deviation of 10 measurements of the 2 microg/l As signal was found to be 1.2%. Results obtained for standard reference materials and water samples are in good agreement with the certified values and those obtained by ICP-MS

Journal Article↗

Arsenic residues in predatory birds from an area of Britain with naturally and anthropogenically elevated arsenic levels.

Birds of prey forage over large areas and so might be expected to accumulate contaminants which are elevated but heterogeneously distributed in the general environment. The aim of this study was to test the hypothesis that arsenic levels in raptors from a region with elevated environmental arsenic concentrations were higher than those in birds from an uncontaminated part of Britain. Arsenic concentrations in the liver, kidney and muscle of kestrels, Falco tinnunculus, sparrowhawks, Accipiter nisus, and barn owls, Tyto alba, from south-west (SW) England, an area with naturally and anthropogenically (through mining) elevated environmental arsenic concentrations, were compared with those in birds from SW Scotland, where no such geochemical anomaly exists. Arsenic residues in kestrels from SW England were approximately three times greater than those in birds from SW Scotland for the three tissue types analysed. This was not the case for the other species in which arsenic residues were similar in birds from both regions. It is suggested that differences between species in both diet and arsenic metabolism could explain why kestrels have elevated arsenic tissue burdens in response to general environmental contamination but sparrowhawks and barn owls do not.

Journal Article↗