Toxicokinetics of (3H)Microcystin-LR in Mice

The distribution, excretion, and metabolism of (microcystin-LR MCYST- LR, sublethal, iv) were measured in mice. Plasma elimination was biexponential with alpha and beta phase half-lives of 0.8 and 6.9 min, respectively. The apparent volume of distribution of the Beta-phase was 10 ml and the bioavailability was 1036 pmol min/ml. At 60 min, liver contained 67% of dose and the amount of hepatic radioactivity did not change through 6 days. Excretion of radiolabel, measured through 6 days, accounted for 23.7 of the dose, with 9.2 an 14.5% in urine and feces, respectively. Approximately 60% of the urine and fecal radiolabel was parent. Hepatic cytosol, which contained 70% of hepatic radiolabel, was prepared for HPLC analysis by heat denaturation, pronase treatment, and C-18 Sep Pak extraction. One hour post exposure, 35% of the radiolabel was insoluble or C-18 Sep Pak-bound; 43% was associated with a peak of retention time (rt) 6.6 min, and 16% with parent. (JES)