1.Inhalation toxicity of brevetoxin 3 in rats exposed for twenty-two days.
Benson JM1, Hahn FF, March TH, McDonald JD, Gomez AP, Sopori MJ, Bourdelais AJ, Naar J, Zaias J, Bossart GD, Baden DG. Environ Health Perspect. 2005 May;113(5):626-31.
Brevetoxins are potent neurotoxins produced by the marine dinoflagellate Karenia brevis. Exposure to brevetoxins may occur during a K. brevis red tide when the compounds become aerosolized by wind and surf. This study assessed possible adverse health effects associated with inhalation exposure to brevetoxin 3, one of the major brevetoxins produced by K. brevis and present in aerosols collected along beaches affected by red tide. Male F344 rats were exposed to brevetoxin 3 at 0, 37, and 237 microg/m3 by nose-only inhalation 2 hr/day, 5 days/week for up to 22 exposure days. Estimated deposited brevetoxin 3 doses were 0.9 and 5.8 microg/kg/day for the low- and high-dose groups, respectively. Body weights of the high-dose group were significantly below control values. There were no clinical signs of toxicity. Terminal body weights of both low- and high-dose-group rats were significantly below control values. Minimal alveolar macrophage hyperplasia was observed in three of six and six of six of the low- and high-dose groups, respectively.
2.Distribution of Brevetoxin to Lipoproteins in human plasma.
Woofter RT1, Ramsdell JS. Toxicon. 2007 Jun 1;49(7):1010-8. Epub 2007 Feb 8.
To better understand the distribution of brevetoxins in lipoproteins, including their role in tissue delivery and toxin elimination in humans, we examined the interaction of brevetoxin congener PbTx-3 with human lipoproteins. In a scintillation proximity assay (SPA) and microtiter equilibrium dialysis, brevetoxin bound linearly to purified human high density, low density, and very low density lipoproteins (HDL, LDL, and VLDL). Both methods demonstrated higher binding capacity per weight for HDL over the other lipoproteins; approximately 50% higher with SPA and 100% higher with equilibrium dialysis. The preferential binding of brevetoxin to HDL particles is consistent with the higher surface to volume ratio of these particles and the association of the toxin with the surface phospholipid/cholesterol domain of the lipoprotein particle. Lipoprotein components were next separated from a well-characterized human plasma sample to determine the mass distribution of brevetoxin within plasma.
3.Effects of a red-tide toxin on fish hearing.
Lu Z1, Tomchik SM. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2002 Nov;188(10):807-13. Epub 2002 Nov 13.
Red tides are formed from blooms of marine algae. Among them, the dinoflagellate ( Karenia brevis) that is responsible for Florida red tides can release many types of natural toxins, which cause massive kills of marine animals, including endangered species, and threaten human health. This study was to investigate whether or not a neurotoxin, brevetoxin-3, purified from Florida red tides affects hearing sensitivity of a teleost fish, the goldfish ( Carassius auratus). LD(50) of the goldfish that were intraperitoneally injected with brevetoxin-3 was 0.068 microg g(-1). Evoked auditory brainstem responses were recorded, and hearing threshold was determined using a correlation method. By comparing thresholds of fish before and after a sublethal-dose injection (0.064 microg g(-1)) of the toxin, we found that brevetoxin-3 significantly reduces auditory sensitivity up to 9 dB at low frequencies (100 Hz and 500 Hz), but not at a high frequency (2,000 Hz).
4.Identification of a rapid detoxification mechanism for brevetoxin in rats.
Radwan FF1, Wang Z, Ramsdell JS. Toxicol Sci. 2005 Jun;85(2):839-46. Epub 2005 Mar 2.
We examined detoxification of brevetoxin in rats through metabolic activities and key elimination routes by analyzing samples from individual rats exposed to two brevetoxin congeners (PbTx-2 and PbTx-3). Brevetoxins were detected by radioimmunoassay in methanolic extracts of blood within 1 h post intraperitoneal (ip) administration. The toxin assay response was about three times higher in PbTx-2-treated rats versus the same dose (180 microg/kg) of PbTx-3. This difference persisted for up to 8 h postexposure. When the blood samples were reextracted with 20% methanol to enhance recovery of potential polar brevetoxin metabolites, 25-fold higher assay activity was present in the PbTx-2-treated rats. Analysis of urine from the same animals identified 7-fold more activity in the PbTx-2-treated rats that accumulated over the course of 24 h. Radioimmunoassay-guided high performance liquid chromatographic analysis of urine from PbTx-2-treated rats yielded three major peaks of activity.