Studies on pharmacokinetics of arsenicals in rats

Abstract

105 male Wistar rats weighing 80±1 g were divided into four groups, five rats to a cage. Arsenic was in all cases administered as a single daily dose per os with catheter, and three groups (75 rats) were administered solutions of sodium arsenite amounting to either 10μgAs, 50 μgAs or 100 μgAs/day continuously for 100 days. The fourth group (30 rats) served as the control. For the determination of arsenic concentrations in rat organs, five rats from each group were sacrificed at days 0 (control group only), 20, 40, 60, 80 and 100. The amounts of arsenic excreted in the feces and urine were checked between every third and fourth day. The amounts of arsenic excreted in the urine of control rats showed a constant level of about 30% of ingested total arsenic (contained naturally in a standard diet). The group administered 10 μgAs/day excreted 13% of the administered arsenic, which increased to 25% as the duration of administration increased. The groups administered 50 μgAs/day and 100 μgAs/day excreted from 5 to 15% of the administered arsenic. The amount of arsenic excreted in feces of control rats was almost equal to that in urine (approximately 30%). At early stage, rats administered arsenic excreted lesser amounts of arsenic (approximately 17 ~ 22%) than the controls (approximately 30%). However, arsenic excretion ratios increased to about 30% as the study period progressed. The average arsenic level in the whole blood of the controls at day 0 was 1.8 ppm, increasing to 7.8 ppm after 100 days. Most of the arsenic in blood is absorbed by erythrocytes. After arsenic was administered, it accumulated in blood at high levels. The concentrations of arsenic in blood were higher for subjects than for controls. Arsenic accumulation in rats organs was observed for both subject and control groups rats except in the case of the skull of the 10μgAs/day and control groups. High concentrations of arsenic in the lungs, heart, kidneys, spleen, liver, testes, brain, muscles, skull and the hair from the experimental group were found when compared to those of control. The spleen, liver, kidneys and the lungs showed the highest concentrations of arsenic of all examined viscera. There were high correlations between arsenic concentrations in body hair and in viscera. Therefore, visceral arsenic concentrations may be hypothesized by examining the levels found in body hair alone.