Blood Arsenic Concentrations Research Articles

Concentration and chemical status of arsenic in the blood of pregnant hamsters during critical embryogenesis: 1. Subchronic exposure to arsenate utilizing constant rate administration

We have determined the concentration, availability, and chemical status of radiolabeled arsenic in the blood of pregnant hamsters at the beginning (morning of Day 8) and the end (morning of Day 9) of the critical period of embryogenesis. Hamster dams were exposed to teratogenic doses of arsenate by means of osmotic minipumps implanted on the morning of Day 6 of the gestation period. Whole blood arsenic concentrations were the same for 48 and 72 hr postimplant. The arsenic concentration of plasma equaled that of red cells. Plasma arsenic was not bound to macromolecules and had the same chemical status 48 and 72 hr postimplant. Arsenate was the dominant form (67% of the total). However, the presence of dimethylarsinic acid and arsenite indicates that the pentavalent species was metabolized. Red cell arsenic was bound to macromolecules in the cell sap. Seventy percent of red cell sap arsenic was dialyzable 48 hr postimplant, but only 56% 72 hr postimplant. Arsenate was the dominant dialyzable red cell species on Day 8 and arsenite was the major dialyzable form on Day 9. Our findings demonstrate a relationship between the maternal blood concentration and chemical status of arsenic and the presence of malformations resulting from a constant rate exposure of pregnant hamsters to arsenate via the osmotic minipump.

Comparative pulmonary toxicity of gallium arsenide, gallium(III) oxide, or arsenic(III) oxide intratracheally instilled into rats

The relative toxicity of gallium arsenide (GaAs) and its metal oxides was assessed by intratracheally instilling particulate suspensions of GaAs (100 mg/kg), equimolar gallium as Ga 2O 3 (65 mg/kg), or a maximally tolerated nonlethal dose of arsenic as As 2O 3 (17 mg/kg). Two weeks after dosing, five rats from each group were randomly selected for the biochemical determination of lung lipid, protein, DNA, and collagen (4-hydroxyproline; 4-HP) content. The pulmonary retention of gallium and /or arsenic and the concentration of these metals in blood were also determined. Lungs from the remaining rats ( n = 3) were examined histopathologically. Pulmonary exposure to Ga 2O 3 particulates significantly ( p < 0.05) increased the total lipid content of lungs relative to that observed in the vehicle-treated control animals. This response appeared to be associated with the pulmonary retention of gallium particulates ( x = 36% of the gallium dose). In contrast, As 2O 3 particulates were not retained in the lung. Blood arsenic concentrations were 36 ppm which represented 20% of the total arsenic administered. Treatment with As 2O 3 significantly elevated lung dry weight as well as protein, DNA, and 4-HP content. These data suggest that As 2O 3 induced an acute fibrogenic response. The intratracheal instillation of GaAs particulates produced effects similar to those observed with the individual oxides. The total lung content of lipids, protein, and DNA was significantly elevated. These biochemical changes were accompanied by significant increases in lung dry weight and lung wet weight. Lungs from rats receiving GaAs particulates retained 44% of the dose as gallium and 28% of the dose as arsenic at the end of the 14-day study. Blood arsenic concentrations were 44 ppm (7% of the arsenic dose) while gallium was not detected in blood at this time. The primary histopathological observations 14 days after the intratracheal instillation of all metal particulates were an inflammatory response and pneumonocyte hyperplasia. The biological severity of these lesions, in descending order, was GaAs > As 2 O 3 ⪢ Ga 2O 3. It must be noted, however, that As 2O 3 was dosed at 0.25 × moles of GaAs.

In vitro solubility and in vivo toxicity of gallium arsenide

The in vitro solubilities of gallium arsenide (GaAs) and its metal oxides were arsenic(III) oxide > GaAs ⪢ gallium(III) oxide. GaAs dissolution was also dependent upon the type and concentration of buffer anion. The amount of arsenic dissolved in 12 hr by various aqueous media was 0.2 m phosphate buffer ≥ 0.1 m phosphate buffer > Krebs-Hensleit buffer > distilled H 2O > HClKCl buffer. GaAs was apparently soluble under in vivo conditions. Blood arsenic concentrations in rats 14 days after intratracheal instillation of 10, 30, or 100 mg/kg GaAs were 5.5, 14.3, and 53.6 μg/ml, respectively; gallium was not detected at any doses. An increase in lung wet weight at 14 days was dose dependent with these organs retaining 17 to 42% of the dose as gallium or arsenic. Excretion of gallium and arsenic was limited to the feces. Urinary porphyrin concentrations and body weight, monitored as indices of toxicity, were significantly altered over the 14-day study. The analysis of porphyrins revealed that uroporphyrin replaced coproporphyrin as the primary urinary metabolite. Rats receiving 10, 100, or 1000 mg/kg GaAs po exhibited similar signs of toxicity. Blood arsenic concentrations at 14 days were 3.5, 6.8, and 17.6 μg/ml, respectively. Porphyria was increased, and body weight was decreased at 1000 mg/kg GaAs. These values were equivalent to those obtained with an intratracheal dose of 10 to 30 mg/kg GaAs. Our results showed that pulmonary and po exposure to GaAs resulted in systemic arsenic intoxication. The finding that urinary uroporphyrin concentrations were greater than coproporphyrin concentrations may serve as a sensitive indicator for GaAs exposure.

Uptake, distribution and elimination of monosodium methanearsonate following long term oral administration of the herbicide to sheep and goats.

The rate and extent of accumulation and washout of arsenic, during daily oral administration of the herbicide monosodium methanearsonate (MSMA) were evaluated in Iranian dairy sheep and goats. Subjects received a dose of 10 mg of MSMA as arsenic per kg of body weight daily for 28 consecutive days. The total arsenic concentration in blood and milk was measured during and after the period of MSMA administration while arsenic in urine and feces was measured for 10 days following administration of last dosage of MSMA. Arsenic was accumulated slowly during 28 days of MSMA administration and steady states were essentially complete in sheep after 20 days and in goats following 25 days of MSMA administration. Blood arsenic concentration decreased rapidly after termination of MSMA administration. In both test animals, the half-lives of washout were smaller than accumulation. The concentration of arsenic in the urine and feces of both species did not increase significantly over controls and animals were free of arsenic relatively shortly after administration stopped. These data indicate that arsenic from MSMA is mainly absorbed from gastrointestinal tract and is not significantly accumulated in the body. Arsenic is eliminated from body by way of urine and feces with urinary excretion being the most important route.

On the Tissue Distribution and the Excretion of Arsenic in Rats and Rabbits of Administration with Arsenical Compounds

Distribution of arsenic in blood and tissues, and excretion of arsenic in feces and urine after an oral administration of arsenic trioxide (29 mg/kg) or methylarsine sulfide (36 mg/kg) were examined in rats and rabbits. Blood level of arsenic in rats reached the maximum 3 days after a single administration of arsenic trioxide, and decreased at a slow biological half-life of 60 days, but blood concentration of arsenic in rabbits was about 1/80 of that in rats 24 hr after dosing. Distribution of arsenic in rat tissues attained the maximum 2 days, but its content was only 1% of the administered dose. Excretion of arsenic in rat feces was 68.6% during the first 4 days and a trace amount of arsenic was detected in bile. Fecal excretion of arsenic in rabbits was 62.9% and 36.2% during 7 days, respectively, when arsenic trioxide and methylarsine sulfide were given. On the other hand, urinary excretion of arsenic in the rat was only 1.8% of the dose during 30 days after arsenic trioxide administration, but the level of arsenic in rabbit urine was 5.5% and 18.2%, respectively, during 7 days after arsenic trioxide and methylarsine sulfide treatment.

The action of an arsenic pentafluoride—Chlorine trifluoride complex on rats

When the highly reactive fluorinating agent, AsF 5·ClF 3 in ClF 3, designated ACFS, was applied to the clipped skin of the rat, a fourth degree burn of nonspecific type was produced. The entire thickness of the skin and part of the underlying musculature were involved. After 2 weeks, normal healing of the burn was well advanced. In the dosage employed, 30–90 mg, the burn produced by ACFS was sufficient to elicit signs of shock. Activity of the animals was reduced and a considerable degree of hemoconcentration occurred. Apart from the burn itself, other pathologic change was almost entirely absent, Histologic evidence of systemic chemical intoxication could not be adduced. The amount of arsenic present in the skin of the burned area decreased with the passage of time following application of the agent. A concomitant increase in blood arsenic concentration was noted, continuing for at least 48 hours. The levels attained exceeded those seen in rats seriously poisoned with arsenite or lewisite. It was found that the arsenic in the blood of ACFS-burned rats was mainly associated with the erythrocytes, specifically with the hemoglobin. Dialysis experiments indicated that this arsenic was relatively firmly bound. Fractionation of the arsenic compounds present in dialyzates of whole blood from ACFS-burned rats revealed that most of the arsenic was in a pentavalent from, although the presence of a small proportion of trivalent compound was demonstrated. In addition to arsenic, fluorine appeared in the blood of rats after the administration of ACFS to the skin. It has been concluded that the most significant sequelae of the ACFS burn are related to effects on the distribution of body fluids and are not referable to the absorption of toxic arsenic and fluorine compounds.