SUBCHRONIC DISPOSITIONAL AND TOXICOLOGICAL EFFECTS OF ARSENATE ADMINISTERED IN DRINKING-WATER TO MICE

Exposure to the drinking water contaminant arsenate is a daily occurre nce and there are concerns that this exposure may lead to cancer. Alth ough the acute dispositional effects of arsenate have been studied in detail, there is minimal information on the disposition and toxicologi cal effects of it after continuous exposure. The objective of this stu dy was to examine in mice the effect of a 4-wk treatment with arsenate administered in drinking water. Female B6C3F1 mice (3/cage) were hous ed in metabolism cages and given water and food ad libitum. Two groups (A, B) of mice were treated (4 cages/treatment/group) with distilled water (control, C) or water containing 0.025 mg/L (L) or 2.5 mg/L (H) arsenate. Group A was sacrificed on d 28 and plasma and urine samples were taken for determination of clinical chemistry parameters. Liver a nd kidney tissue samples were taken for histopathological analysis. Th e reduced nonprotein sulfhydryl (NPSH) content in several tissues war determined. Group B was gavaged with [As-73]arsenate on d 28 and conti nued the arsenate drinking water exposure for 48 h. Excreta and tissue s were collected and analyzed for As-73. Urine was further analyzed fo r arsenate and its metabolites. There were no effects on the mean dail y amount of water and food consumed, whereas the mean daily urine volu me excreted was significantly elevated by 10% in the H-treated animals compared to C and L. A dose-related hepatic vacuolar degeneration in the liver was observed, but no histological changes were evident in th e kidney. Only clinical chemistry parameters in plasma were altered by the arsenate treatment. Glucose was significantly lower at the H dose compared to C and L, triglycerides were significantly greater in C th an L and H, and creatinine was significantly greater in H than C. Hepa tic NPSH content in the H animals was significantly lower than C and L animals, whereas no effects in lung and kidney were detected. The wei ghts of liver, lung, and kidney, as well as their tissue/body weight r atios, were significantly decreased in the H animals. As-73 was primar ily eliminated in urine, and its elimination was not affected by dose. No effects on the 48-h As-73 cumulative excretion (urine + fecal) wer e detected. The As-73 distribution was low in amount and widely disper sed throughout the animal (<3% of the As-73 dose). The kidney had the highest As-73 concentration of the tissues (0.01% As-73 dose/g tissue) . Dimethylarsinic acid was the major metabolite detected in urine, wit h lower amounts of arsenate, arsenite, and monomethylarsonate. There w ere no differences between the treatment groups in the amount of urina ry metabolites after a single dose of [As-73]arsenate. Several toxicol ogical effects were observed in animals administered arsenate in drink ing water, but no changes in the disposition of this arsenical were de tected at the doses used in this study.