Uptake, tissue distribution, and excretion of brevetoxin 3 administered torats by intratracheal instillation

Brevetoxins are cyclic polyether neurotoxins produced by the marine dinofla gellate Ptychodiscus brevis. Blooms of P. brevis (red tides) are toxic to f ish, marine mammals, and humans. Humans exposed to seaspray aerosols contai ning brevetoxins may experience respiratory tract irritation. Because a maj or route of human exposure to brevetoxins is via the respiratory trace, the objective of this study was to examine the toxicokinetics of brevetoxin 3 (PbTx-3) administered to the lung by intratracheal instillation. Twenty-one male F344/CrI BR rats, 12 wk of age, were administered H-3-PbTx-3 (1 mu Ci , 6.6 mu g PbTx-3/kg) by intratracheal instillation. Groups of 3 rats were sacrificed at 0.5, 3, 6, 24, 48, and 96 h after exposure, and tissues were collected. Three additional rats were placed in glass metabolism cages for collection of urine and feces over a 7-d period. PbTx-3-associated activity was cleared rapidly from the lung and distributed throughout the body, chi efly to the carcass, intestines, and liver. Blood, brain, and fat contained the lowest percentages of the administered dose. Although a majority of th e PbTx-3 was cleared rapidly from lung, liver, and kidneys, approximately 2 0% of the initial concentration present in each organ was retained for 7 d. Concentrations of PbTx-3 in brain and fat were low, but remained relativel y constant over time. Approximately twice as much PbTx-3-associated activit y was excreted in feces than in urine, with the majority of excretion occur ring within 48 h after instillation. The results of this study indicate tha t over 80% of the PbTx-3 is rapidly absorbed from the lung to the blood and distributed to all tissues. The tissues containing the greatest amount of PbTx-3-associated activity reflect the compound's site of deposition, stora ge compartment, and major route of metabolism and excretion. These results illustrate that brevetoxin exposure by the respiratory route results in sys temic distribution of brevetoxin and suggest that the initial respiratory i rritation and bronchoconstriction may only be a part of the overall toxicol ogical consequences associated with brevetoxin inhalation.