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Keywords:

  • distribution elimination;
  • cylindrospermopsin mouse

Abstract

Radiolabelled 14C cylindrospermopsin (CYN) has been prepared and used to investigate the distribution and excretion of CYN in vivo in male Quackenbush mice. At a dose of 0.2 mg/kg (i.e., approx. median lethal dose) the following mean (SD) urinary and faecal recoveries (cumulative) were obtained, respectively: (0–6 hours, n=4) 48.2 (29.3)%, 11.9 (21.4)%; (0–12 hours, n=12) 66.0 (27.1)%, 5.7 (5.6)%; (0–24 hours, n=12) 68.4 (26.7)%, 8.5 (8.1)%. Mean (SD) recoveries from livers at 6 hours were 20.6 (6.4)% (n=4), at 48 hours 13.1 (7.7)% (n=8), and 5–7 days were 2.1 (2.1)% (n=8). A substantial amount (up to 23%) can be retained in the liver for up to 48 hours with a lesser amount retained in the kidneys. The excretion patterns show substantial interindividual variability between predominantly faecal or urinary excretion, but these patterns are not related in any simple manner to the outcome in terms of toxicity. There is at least one methanol-extractable metabolite as well as a nonmethanol-extractable metabolite in the liver. The methanol-extractable metabolite was not found in the kidney and is more hydrophilic than CYN itself on reverse phase. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 498–505, 2001