Adult female Fisher 344 rats received
drinking water containing 0, 4, 40, 100, or 200 parts per million of
dimethylarsinic acid or 100 parts per million of
arsenate for 14 days. Urine was collected during the last 24 h of exposure. Tissues were then taken for analysis of dimethylated and trimethylated
arsenicals; urines were analyzed for these
arsenicals and their thiolated derivatives. In
dimethylarsinic acid-treated rats, highest concentrations of dimethylated
arsenic were found in blood. In lung, liver, and kidney, concentrations of dimethylated
arsenic exceeded those of trimethylated species; in urinary bladder and urine, trimethylated
arsenic predominated.
Dimethylthioarsinic acid and
trimethylarsine sulfide were present in urine of
dimethylarsinic acid-treated rats. Concentrations of dimethylated
arsenicals were similar in most tissues of
dimethylarsinic acid- and
arsenate-treated rats, including urinary bladder which is the target for
dimethylarsinic acid-induced
carcinogenesis in the rat. Mean concentration of dimethylated
arsenic was significantly higher (P<0.05) in urine of
dimethylarsinic acid-treated rats than in
arsenate-treated rats, suggesting a difference between treatment groups in the flux of dimethylated
arsenic through urinary bladder. Concentrations of trimethylated
arsenic concentrations were consistently higher in
dimethylarsinic acid-treated rats than in
arsenate-treated rats; these differences were significant (P<0.05) in liver, urinary bladder, and urine. Concentrations of
dimethylthioarsinic acid and
trimethylarsine sulfide were higher in urine from
dimethylarsinic acid-treated rats than from
arsenate-treated rats.
Dimethylarsinic acid is extensively metabolized in the rat, yielding significant concentrations of trimethylated species and of thiolated derivatives. One or more of these metabolites could be the species causing alterations of cellular function that lead to
tumors in the urinary bladder.