Notes: ABT-594 [(R)-5-(2-azetedinylmethoxy)-2-chloropyridine mono-tosylate salt] is a neuronal nicotinic acetylcholine receptor (nAChR) agonist with antinociceptive activity in rodent pain models. Whereas the binding affinity of ABT-594 at α4β2-containing nAChRs is comparable to that of (±)-epibatidine, ABT-594 has lower affinity than (±)-epibatidine at α3-containing nAChRs. Similarly, ABT-594 is approximately equivalent to (±)-epibatidine in a Ca2+ flux assay in K-177 cells that express 04132 nAChRs but less potent than (±)-epibatidine in the IMR-32 (α3-containing) cell line. ABT-594 is active in a variety of rodent models of acute thermal (mouse hot-plate, rat thermal paw withdrawal), persistent chemical (mouse abdominal constriction, rat formalin) and neuropathic (diabetic neuropathy and Chung spinal nerve ligation in rats) pain. Effects of ABT-594 on acute thermal pain appear to be mediated centrally and may involve activation of descending inhibition originating in the brainstem. ABT-594 decreases responses of wide dynamic range neurons in the dorsal lumbar spinal cord to noxious thermal and mechanical stimuli but does not alter responses of these neurons to innocuous stimuli. ABT-594 has plasma elimination half life ranging from 〈 0.5 h in mice to 4.7 h in dogs and readily penetrates the CNS. Oral bioavailability ranges from 35 to 80% in a variety of species. In rats, the majority of ABT-594 is excreted in the urine after both oral and intravenous administration, and parent drug accounts for better than 75% of total radioactivity in plasma after administration of labeled ABT-594 (AUC0–12)

Notes: A proof-of-concept experiment was devised to determine if pharmaceuticals and other organic waste water compounds (OWCs), as well as pathogens, found in treated effluent could be transported through a 2.4 m soil column and, thus, potentially reach ground water under recharge conditions similar to those in arid or semiarid climates. Treated effluent was applied at the top of the 2.4 m long, 32.5 cm diameter soil column over 23 days. Samples of the column inflow were collected from the effluent storage tank at the beginning (Tbegin) and end (Tend) of the experiment, and a sample of the soil column drainage at the base of the column (Bend) was collected at the end of the experiment. Samples were analyzed for 131 OWCs including veterinary and human antibiotics, other prescription and nonprescription drugs, widely used household and industrial chemicals, and steroids and reproductive hormones, as well as the pathogens Salmonella and Legionella. Analytical results for the two effluent samples taken at the beginning (Tbegin) and end (Tend) of the experiment indicate that the number of OWCs detected in the column inflow decreased by 25% (eight compounds) and the total concentration of OWCs decreased by 46% while the effluent was in the storage tank during the 23-day experiment. After percolating through the soil column, an additional 18 compounds detected in Tend (67% of OWCs) were no longer detected in the effluent (Bend) and the total concentration of OWCs decreased by more than 70%. These compounds may have been subject to transformation (biotic and abiotic), adsorption, and (or) volatilization in the storage tank and during travel through the soil column. Eight compounds—carbamazapine; sulfamethoxazole; benzophenone; 5-methyl-1H-benzotriazole; N, N-diethyltoluamide; tributylphosphate; tri(2-chloroethyl) phosphate; and cholesterol—were detected in all three samples indicating they have the potential to reach ground water under recharge conditions similar to those in arid and semiarid climates. Results from real-time polymerase chain reactions demonstrated the presence of Legionella in all three samples. Salmonella was detected only in Tbegin, suggesting that the bacteria died off in the effluent storage tank over the period of the experiment. This proof-of-concept experiment demonstrates that, under recharge conditions similar to those in arid or semiarid climates, some pharmaceuticals, pathogens, and other OWCs can persist in treated effluent after soil-aquifer treatment.

Notes: Ground water samples collected from the Norman Landfill research site in central Oklahoma were analyzed as part of the U.S. Geological Survey (USGS) Toxic Substances Hydrology Program's national reconnaissance of pharmaceuticals and other organic waste water contaminants (OWCs) in ground water. Five sites, four of which are located downgradient of the landfill, were sampled in 2000 and analyzed for 76 OWCs using four research methods developed by the USGS. OWCs were detected in water samples from all of the sites sampled, with 22 of the 76 OWCs being detected at least once. Cholesterol (a plant and animal steroid), was detected at all five sites and was the only compound detected in a well upgradient of the landfill. N,N-diethyltoluamide (DEBT used in insect repellent) and tri(2-chloroethyl) phosphate (fire-retardant) were detected in water samples from all four sites located within the landfill-derived leachate plume. The sites closest to the landfill had more detections and greater concentrations of each of the detected compounds than sites located farther away. Detection of multiple OWCs occurred in the four sites located within the leachate plume, with a minimum of four and a maximum of 17 OWCs detected. Because the landfill was established in the 1920s and closed in 1985, many compounds detected in the leachate plume were likely disposed of decades ago. These results indicate the potential for long-term persistence and transport of some OWCs in ground water.