Human use pharmaceuticals in the estuarine environment: a survey of the Chesapeake Bay, Biscayne Bay, and Gulf of the Farallones

The assessment of emerging risks in the aquatic environment is a major concern and focus of environmental science (Daughton and Ternes, 1999). One significant class of chemicals that has received relatively little attention until recently are the human use pharmaceuticals. In 2004, an estimated 2.6 billion prescriptions were written for the top 300 pharmaceuticals in the U.S. (RxList, 2005). Mellon et al. (2001) estimated that 1.4 million kg of antimicrobials are used in human medicine every year. The use of pharmaceuticals is also estimated to be on par with agrochemicals (Daughton and Ternes, 1999). Unlike agrochemicals (e.g., pesticides) which tend to be delivered to the environment in seasonal pulses, pharmaceuticals are continuously released through the use/excretion and disposal of these chemicals, which may produce the same exposure potential as truly persistent pollutants. Human use pharmaceuticals can enter the aquatic environment through a number of pathways, although the main one is thought to be via ingestion and subsequent excretion by humans (Thomas and Hilton, 2004). Unused pharmaceuticals are typically flushed down the drain or wind up in landfills (Jones et al. 2001).

Concurrent exposure of bottlenose dolphins (Tursiops truncatus) to multiple algal toxins in Sarasota Bay, Florida, USA

Sentinel species such as bottlenose dolphins (Tursiops truncatus) can be impacted by large-scale mortality events due to exposure to marine algal toxins. In the Sarasota Bay region (Gulf of Mexico, Florida, USA), the bottlenose dolphin population is frequently exposed to harmful algal blooms (HABs) of Karenia brevis and the neurotoxic brevetoxins (PbTx; BTX) produced by this dinoflagellate. Live dolphins sampled during capture-release health assessments performed in this region tested positive for two HAB toxins; brevetoxin and domoic acid (DA). Over a ten-year study period (2000–2009) we have determined that bottlenose dolphins are exposed to brevetoxin and/or DA on a nearly annual basis (i.e., DA: 2004, 2005, 2006, 2008, 2009; brevetoxin: 2000, 2004, 2005, 2008, 2009) with 36% of all animals testing positive for brevetoxin (n = 118) and 53% positive for DA (n = 83) with several individuals (14%) testing positive for both neurotoxins in at least one tissue/fluid. To date there have been no previously published reports of DA in southwestern Florida marine mammals, however the May 2008 health assessment coincided with a Pseudo-nitzschia pseudodelicatissima bloom that was the likely source of DA observed in seawater and live dolphin samples. Concurrently, both DA and brevetoxin were observed in common prey fish. Although no Pseudo-nitzschia bloom was identified the following year, DA was identified in seawater, fish, sediment, snails, and dolphins. DA concentrations in feces were positively correlated with hematologic parameters including an increase in total white blood cell (p = 0.001) and eosinophil (p<0.001) counts. Our findings demonstrate that dolphins within Sarasota Bay are commonly exposed to two algal toxins, and provide the impetus to further explore the potential long-term impacts on bottlenose dolphin health.

Brevetoxin in two planktivorous fishes after exposure to Karenia brevis: implications for food-web transfer to bottlenose dolphins

Brevetoxin uptake was analyzed in 2 common planktivorous fish that are likely foodweb vectors for dolphin mortality events associated with brevetoxin-producing red tides. Fish were exposed to brevetoxin-producing Karenia brevis for 10 h under conditions previously reported to produce optimal uptake of toxin in blood after oral exposure. Striped mullet Mugil cephalus were exposed to a low dose of brevetoxin, and uptake and depuration by specific organs were evaluated over a 2 mo period. Atlantic menhaden Brevoortia tyrannus specimens were used to characterize a higher brevetoxin dose uptake into whole body components and evaluate depuration over 1 mo. We found a high uptake of toxin by menhaden, with a body to water ratio of 57 after a 10 h exposure and a slow elimination with a half life (t1/2) of 24 d. Elimination occurred rapidly from the intestine (t1/2 < 1 wk) and muscle (t1/2 ≈ 1 wk) compartments and redistributed to liver which continued to accumulate body stores of toxin for 4 wk. The accumulation and elimination characteristics of the vectoring capacity of these 2 fish species are interpreted in relation to data from the Florida Panhandle dolphin mortality event of 2004. We show that due to slow elimination rate of brevetoxin in planktivorous fish, brevetoxin-related dolphin mortality events may occur without evidence of a concurrent harmful algal bloom event.

Immunomodulatory effects of domoic acid differ between In vivo and In vitro exposure in mice

The immunotoxic potential of domoic acid (DA), a well-characterized neurotoxin, has not been fully investigated. Phagocytosis and lymphocyte proliferation were evaluated following in vitro and in vivo exposure to assay direct vs indirect effects. Mice were injected intraperitoneally with a single dose of DA (2.5 µg/g b.w.) and sampled after 12, 24, or 48 hr. In a separate experiment, leukocytes and splenocytes were exposed in vitro to 0, 1, 10, or 100 µM DA. In vivo exposure resulted in a significant increase in monocyte phagocytosis (12-hr), a significant decrease in neutrophil phagocytosis (24-hr), a significant decrease in monocyte phagocytosis (48-hr), and a significant reduction in T-cell mitogen-induced lymphocyte proliferation (24-hr). In vitro exposure significantly reduced neutrophil and monocyte phagocytosis at 1 µM. B- and T-cell mitogen-induced lymphocyte proliferation were both significantly increased at 1 and 10 µM, and significantly decreased at 100 µM. Differences between in vitro and in vivo results suggest that DA may exert its immunotoxic effects both directly and indirectly. Modulation of cytosolic calcium suggests that DA exerts its effects through ionotropic glutamate subtype surface receptors at least on monocytes. This study is the first to identify DA as an immunotoxic chemical in a mammalian species.